2017-09-26T21:39:22ZA human clinical trial using ultrasound and microbubbles to enhance gemcitabine treatment of inoperable pancreatic cancerhttp://hdl.handle.net/1956/16668
A human clinical trial using ultrasound and microbubbles to enhance gemcitabine treatment of inoperable pancreatic cancer
Dimcevski, Georg Gjorgji; Kotopoulis, Spiros; Bjånes, Tormod Karlsen; Hoem, Dag; Schjøtt, Jan; Gjertsen, Bjørn Tore; Biermann, Martin; Molven, Anders; Sorbye, Halfdan; McCormack, Emmet; Postema, Michiel; Gilja, Odd Helge
Journal article
<p>Background: The primary aim of our study was to evaluate the safety and potential toxicity of gemcitabine combined with microbubbles under sonication in inoperable pancreatic cancer patients. The secondary aim was to evaluate a novel image-guided microbubble-based therapy, based on commercially available technology, towards improving chemotherapeutic efficacy, preserving patient performance status, and prolonging survival.</p>
<p>Methods: Ten patients were enrolled and treated in this Phase I clinical trial. Gemcitabine was infused intravenously over 30 min. Subsequently, patients were treated using a commercial clinical ultrasound scanner for 31.5 min. SonoVue&reg; was injected intravenously (0.5 ml followed by 5 ml saline every 3.5 min) during the ultrasound treatment with the aim of inducing sonoporation, thus enhancing therapeutic efficacy.</p>
<p>Results: The combined therapeutic regimen did not induce any additional toxicity or increased frequency of side effects when compared to gemcitabine chemotherapy alone (historical controls). Combination treated patients (n = 10) tolerated an increased number of gemcitabine cycles compared with historical controls (n = 63 patients; average of 8.3 &plusmn; 6.0 cycles, versus 13.8 &plusmn; 5.6 cycles, p = 0.008, unpaired t-test). In five patients, the maximum tumour diameter was decreased from the first to last treatment. The median survival in our patients (n = 10) was also increased from 8.9 months to 17.6 months (p = 0.011).</p>
<p>Conclusions: It is possible to combine ultrasound, microbubbles, and chemotherapy in a clinical setting using commercially available equipment with no additional toxicities. This combined treatment may improve the clinical efficacy of gemcitabine, prolong the quality of life, and extend survival in patients with pancreatic ductal adenocarcinoma.</p>
2016-12-01T00:00:00ZPlasma free choline, betaine and cognitive performance: the Hordaland Health Studyhttp://hdl.handle.net/1956/16664
Plasma free choline, betaine and cognitive performance: the Hordaland Health Study
Nurk, Eha; Refsum, Helga; Bjelland, Ingvar; Drevon, Christian A; Tell, Grethe S; Ueland, Per Magne; Vollset, Stein Emil; Engedal, Knut Arne; Nygaard, Harald A.; Smith, David A
Journal article
Choline and betaine are nutrients involved in one-carbon metabolism. Choline is essential for neurodevelopment and brain function. We studied the associations between cognitive function and plasma concentrations of free choline and betaine. In a cross-sectional study, 2195 subjects (55 % women), aged 70–74 years, underwent extensive cognitive testing including the Kendrick Object Learning Test (KOLT), Trail Making Test (part A, TMT-A), modified versions of the Digit Symbol Test (m-DST), Block Design (m-BD), Mini-Mental State Examination (m-MMSE) and Controlled Oral Word Association Test (COWAT). Compared with low concentrations, high choline (>8·4 μmol/l) was associated with better test scores in the TMT-A (56·0 v. 61·5, P= 0·004), m-DST (10·5 v. 9·8, P= 0·005) and m-MMSE (11·5 v. 11·4, P= 0·01). A generalised additive regression model showed a positive dose–response relationship between the m-MMSE and choline (P= 0·012 from a corresponding linear regression model). Betaine was associated with the KOLT, TMT-A and COWAT, but after adjustments for potential confounders, the associations lost significance. Risk ratios (RR) for poor test performance roughly tripled when low choline was combined with either low plasma vitamin B12 ( ≤ 257 pmol/l) concentrations (RRKOLT= 2·6, 95 % CI 1·1, 6·1; RRm-MMSE= 2·7, 95 % CI 1·1, 6·6; RRCOWAT= 3·1, 95 % CI 1·4, 7·2) or high methylmalonic acid (MMA) ( ≥ 3·95 μmol/l) concentrations (RRm-BD= 2·8, 95 % CI 1·3, 6·1). Low betaine ( ≤ 31·1 μmol/l) combined with high MMA was associated with elevated RR on KOLT (RRKOLT= 2·5, 95 % CI 1·0, 6·2). Low plasma free choline concentrations are associated with poor cognitive performance. There were significant interactions between low choline or betaine and low vitamin B12 or high MMA on cognitive performance.
2013-02-01T00:00:00ZDeformation and initial stability in hip arthroplasty. Effect of neck geometry and fixation – an experimental cadaver studyhttp://hdl.handle.net/1956/16642
Deformation and initial stability in hip arthroplasty. Effect of neck geometry and fixation – an experimental cadaver study
Enoksen, Cathrine Harstad
Doctoral thesis
<p>Introduction: The search for and development of the optimal joint implant include
preclinical testing. Restoration of the individual and natural biomechanics in the hip
joint is a central goal in hip arthroplasty, and can be achieved by varying neck length,
version and angle. Modular necks are one way to achieve these adjustments despite a
growing concern regarding their outcome. In hip arthroplasty, the implants can be
attached to the bone with or without cement. Both methods have achieved good
clinical results. In this thesis, the effect of varying the femoral neck angle and length
was tested in an experimental setup simulating everyday activities. Further, a
cemented and an uncemented femoral stem with similar geometrical shape were
compared in a preclinical setup.</p>
<p>Methods: All implants were tested in human cadaver femurs by loading in a hip
simulator in single leg stance and stair climbing activity. Changes in deformation
pattern of the proximal femur were measured by strain gauges. Initial stability of the
femoral stems was investigated using a micromotion jig. The effect on the deformation
pattern and initial stability was studied when the neck version, angle and length were
varied, due to either an eccentric femoral head or a modular neck. The deformation
pattern and initial stability of a cemented and an uncemented stem of similar geometry
were compared.</p>
<p>Results: Strain was reduced in the proximal femur for all implants tested, especially
proximally on the medial side, compared to the intact femur. Increased offset
combined with retroversion or reduced neck–shaft angle in an eccentric femoral head
gave significantly increased strain values compared to the standard situation. All three
eccentric femoral head configurations gave overall small micromotion of the femoral
stem; up to 40 μm.
When testing the modular necks, the varus neck increased the micromotion up to 60
μm. Micromotion was significantly higher during stair climbing compared to single
leg loading, and for distal level compared to proximal level in all modular necks. The short neck had higher loss of strain in distal position on the lateral side, and the
retroverted neck retained more strain proximal medially.
The cemented stem had slightly higher strains than the uncemented stem on the medial
side, while uncemented stem had higher strains on the lateral side of the proximal
femur. The differences were small, but statistically significant.</p>
<p>Conclusion: Varying the femoral neck version, angle and length by either an eccentric
femoral head or a modular neck gave some variations in cortical strains in the
proximal femur compared to a standard design. However, the differences might be too
small to have any clinical significance. The initial stability was acceptable for the
tested implants when varying the femoral neck angle and length.
The cemented stem was more stable than the uncemented stem, as expected. However,
both stems had small micromotions at the bone-implant interface, and in a range, that
is not expected to have a negative impact on long-term stability.</p>
2017-06-08T00:00:00ZTargeted temperature management in cardiac arrest: survival evaluated by propensity score matchinghttp://hdl.handle.net/1956/16621
Targeted temperature management in cardiac arrest: survival evaluated by propensity score matching
Buanes, Eirik Aines; Hufthammer, Karl O.; Langørgen, Jørund; Guttormsen, Anne-Berit; Heltne, Jon-Kenneth
Journal article
Background: Targeted temperature management in cardiac arrest was introduced following evidence of
increased survival from two controlled trials published in 2002. We wanted to investigate whether
the introduction of targeted temperature management to clinical practice had increased the survival
of cardiac arrest patients at Haukeland University Hospital, Norway.
Methods: We included 336 unresponsive patients admitted to the emergency department between
December 2003 and December 2008 with return of spontaneous circulation following out-of-hospital
cardiac arrest in the analysis. A propensity score model was developed to evaluate the survival of
patients receiving intensive care treatment including targeted temperature management, compared
with intensive care treatment not including targeted temperature management.
Results: Estimation of the treatment effect revealed an increase of 57 days (95% CI: 12–103, p =
0.01) in restricted mean survival during the first year after cardiac arrest for intensive care
treatment including targeted temperature management.
Discussion: As with all observational studies, bias is probable. However, propensity score
methodology has been used in order to reduce bias and establish causality. Although residual
confounding is likely, our interpretation is that TTM increased survival for comatose OHCA patients
in our hospital because survival increased well beyond the level of significance.
Conclusion: The introduction of targeted temperature management to clinical practice is likely to
have increased survival
for unresponsive patients following out-of-hospital cardiac arrest.
2017-01-01T00:00:00ZCardiac Arrest in a Community: Epidemiology, Treatment, and Outcomehttp://hdl.handle.net/1956/16620
Cardiac Arrest in a Community: Epidemiology, Treatment, and Outcome
Buanes, Eirik Aines
Doctoral thesis
<p><strong>Background:</strong> Incidence and mortality from sudden cardiac arrest is high, making it a
prevalent cause of death. Both incidence and survival rates show great variability
between populations. In order to improve survival from sudden cardiac arrest, it is
necessary to view aetiology, treatment effects, and outcome as a whole.</p>
<p><strong>Aim:</strong> To investigate cardiac arrest incidence, treatment, and outcome in one
geographic area during a limited period of time.</p>
<p><strong>Method:</strong> Paper I and Paper II prospectively included consecutive patients suffering
cardiac arrest in one of our local hospitals, or in the geographical area delivering
patients to these hospitals, between 1 December 2008 and 30 November 2009. Paper
I compared out-of-hospital cardiac arrest with in-hospital cardiac arrest in terms of
Utstein characteristics and survival. Paper II compared cognitive function in cardiac
arrest survivors with good neurologic outcome at hospital discharge with an age- and
gender-matched reference population. Paper III retrospectively examined consecutive
out-of-hospital cardiac arrest survivors from December 2003 to December 2008
admitted to the emergency department in a comatose state. Propensity score matching
was used to compare intensive care treatment including targeted temperature
management with intensive care treatment not including targeted temperature
management in regard to survival.</p>
<p><strong>Results:</strong> The incidence was 60.6 per 100.000 person-years for out-of-hospital cardiac
arrest and 41.3 per 100.000 person-years for in-hospital cardiac arrest. Survival to
hospital discharge was 16.2% for in-hospital cardiac arrest and 16.8% for out-ofhospital
cardiac arrest. Pooled mortality from cardiac arrest in our community was
85.0 per 100.000 person-years. Four years after cardiac arrest, 29% of patients had
mild cognitive impairment. Restricted mean survival time increased by 57 days as a
result of targeted temperature management. Standardised mortality ratio was 2.8 for
cardiac arrest survivors over the first four years following hospital discharge,
compared with an age- and gender-matched normal population.</p>
<p><strong>Conclusion:</strong> Survival to hospital discharge was similar between in-hospital and outof-
hospital cardiac arrest. The majority of cardiac arrests occurred out-of-hospital.
Nearly one-third of patients with good cerebral outcome on hospital discharge had
mild cognitive impairment four years after cardiac arrest. Targeted temperature
management increased survival after cardiac arrest.</p>
2017-09-01T00:00:00ZTissue and imaging biomarkers for hypoxia predict poor outcome in endometrial cancerhttp://hdl.handle.net/1956/16366
Tissue and imaging biomarkers for hypoxia predict poor outcome in endometrial cancer
Berg, Anna; Fasmer, Kristine Eldevik; Mauland, Karen Klepsland; Ytre-Hauge, Sigmund; Høivik, Erling Andre; Husby, Jenny Hild Aase; Tangen, Ingvild Løberg; Trovik, Jone; Halle, Mari Kyllesø; Woie, Kathrine; Bjørge, Line; Bjørnerud, Atle; Salvesen, Helga; Werner, Henrica Maria Johanna; Krakstad, Camilla; Haldorsen, Ingfrid S.
Journal article
Hypoxia is frequent in solid tumors and linked to aggressive phenotypes and therapy resistance. We explored expression patterns of the proposed hypoxia marker HIF-1α in endometrial cancer (EC) and investigate whether preoperative functional imaging parameters are associated with tumor hypoxia. Expression of HIF-1α was explored both in the epithelial and the stromal tumor component. We found that low epithelial HIF-1α and high stromal HIF-1α expression were significantly associated with reduced disease specific survival in EC. Only stromal HIF-1α had independent prognostic value in Cox regression analysis. High stromal HIF-1α protein expression was rare in the premalignant lesions of complex atypical hyperplasia but increased significantly to invasive cancer. High stromal HIF-1α expression was correlated with overexpression of important genes downstream from HIF-1α, i.e. VEGFA and SLC2A1 (GLUT1). Detecting hypoxic tumors with preoperative functional imaging might have therapeutic benefits. We found that high stromal HIF-1α expression associated with high total lesion glycolysis (TLG) at PET/CT. High expression of a gene signature linked to hypoxia also correlated with low tumor blood flow at DCE-MRI and increased metabolism measured by FDG-PET. PI3K pathway inhibitors were identified as potential therapeutic compounds in patients with lesions overexpressing this gene signature. In conclusion, we show that high stromal HIF-1α expression predicts reduced survival in EC and is associated with increased tumor metabolism at FDG-PET/CT. Importantly; we demonstrate a correlation between tissue and imaging biomarkers reflecting hypoxia, and also possible treatment targets for selected patients.
2016-09-13T00:00:00ZDefective mitochondrial DNA homeostasis in the substantia nigra in Parkinson diseasehttp://hdl.handle.net/1956/16365
Defective mitochondrial DNA homeostasis in the substantia nigra in Parkinson disease
Dölle, Christian; Flønes, Irene Hana; Sanchez Nido, Gonzalo; Miletic, Hrvoje; Osuagwu, Nelson; Kristoffersen, Stine; Lilleng, Peer Kåre; Larsen, Jan Petter; Tysnes, Ole-Bjørn; Haugarvoll, Kristoffer; Bindoff, Laurence; Tzoulis, Charalampos
Journal article
Increased somatic mitochondrial DNA (mtDNA) mutagenesis causes premature aging in mice, and mtDNA damage accumulates in the human brain with aging and neurodegenerative disorders such as Parkinson disease (PD). Here, we study the complete spectrum of mtDNA changes, including deletions, copy-number variation and point mutations, in single neurons from the dopaminergic substantia nigra and other brain areas of individuals with Parkinson disease and neurologically healthy controls. We show that in dopaminergic substantia nigra neurons of healthy individuals, mtDNA copy number increases with age, maintaining the pool of wild-type mtDNA population in spite of accumulating deletions. This upregulation fails to occur in individuals with Parkinson disease, however, resulting in depletion of the wild-type mtDNA population. By contrast, neuronal mtDNA point mutational load is not increased in Parkinson disease. Our findings suggest that dysregulation of mtDNA homeostasis is a key process in the pathogenesis of neuronal loss in Parkinson disease.
2016-11-22T00:00:00ZDiagnostic accuracy of transabdominal ultrasound in chronic pancreatitishttp://hdl.handle.net/1956/16220
Diagnostic accuracy of transabdominal ultrasound in chronic pancreatitis
Engjom, Trond; Sangnes, Dag André; Havre, Roald Flesland; Erchinger, Friedemann Georg; Pham, Khanh Do-Cong; Haldorsen, Ingfrid S.; Gilja, Odd Helge; Dimcevski, Georg Gjorgji
Journal article
The performance of transabdominal ultrasound (US) in chronic pancreatitis (CP) following the advances in US technology made during recent decades has not been explored. Our aim in this prospective study was to evaluate the diagnostic accuracy of modern abdominal US compared with the Mayo score in CP. One hundred thirty-four patients referred for suspected CP were included in the study. Fifty-four patients were assigned the diagnosis CP. After inclusion, transabdominal US was performed. Ductal features (calculi, dilations and caliber variations, side-branch dilations and hyper-echoic duct wall margins) and parenchymal features (calcifications, cysts, hyper-echoic foci, stranding, lobulation and honeycombing) were recorded. Features were counted and scored according to a weighting system defined at the international consensus meeting in Rosemont, Illinois (Rosemont score). Diagnostic performance indices (95% confidence interval) of US were calculated: The unweighted count of features had a sensitivity of 0.69 (0.54–0.80) and specificity of 0.97 (0.90–1). The Rosemont score had a sensitivity of 0.81 (0.69–0.91) and specificity of 0.97 (0.90–1). Exocrine pancreatic failure was most pronounced in Rosemont groups I and II (p < 0.001). We conclude that using both unweighted and weighted scores, the diagnostic accuracy of modern transabdominal US is good. The extent of pancreatic changes detected by the method is correlated with exocrine pancreatic function.
2017-04-01T00:00:00ZBone cement product and failure in total knee arthroplasty: A follow-up study of 26,147 knee replacements between 1997 and 2013 in Norwayhttp://hdl.handle.net/1956/16199
Bone cement product and failure in total knee arthroplasty: A follow-up study of 26,147 knee replacements between 1997 and 2013 in Norway
Birkeland, Øystein; Espehaug, Birgitte; Havelin, Leif Ivar; Furnes, Ove
Journal article
<p>Background and purpose &mdash; The bone cement market for total knee arthroplasty (TKA) in Norway has been dominated by a few products and distributors. Palacos with gentamicin had a market share exceeding 90% before 2005, but it was then withdrawn from the market and replaced by new slightly altered products. We have compared the survival of TKAs fixated with Palacos with gentamicin with the survival of TKAs fixated with the bone cements that took over the market.</p>
<p>Patients and methods &mdash; Using data from the Norwegian Arthroplasty Register for the period 1997&ndash;2013, we included 26,147 primary TKAs in the study. The inclusion criteria were TKAs fixated with the 5 most used bone cements and the 5 most common total knee prostheses for that time period. 6-year Kaplan-Meier survival probabilities were established for each cement product. The Cox proportional hazards regression model was used to assess the association between bone cement product and revision risk. Separate analyses were performed with revision for any reason and revision due to deep infection within 1 year postoperatively as endpoints. Adjustments were made for age, sex, diagnosis, and prosthesis brand.</p>
<p>Results &mdash; Survival was similar for the prostheses in the follow-up period, between the 5 bone cements included: Palacos with gentamicin, Refobacin Palacos R, Refobacin Bone Cement R (Refobacin BCR), Optipac Refobacin Bone Cement R (Optipac Refobacin BCR), and Palacos R&thinsp;+&thinsp;G.</p>
<p>Interpretation &mdash; According to our findings, the use of the new bone cements led to a survival rate that was as good as with the old bone cement (Palacos with gentamicin).</p>
2017-01-01T00:00:00ZElevated microsatellite alterations at selected tetranucleotides in early-stage colorectal cancers with and without high-frequency microsatellite instability: same, same but different?http://hdl.handle.net/1956/16190
Elevated microsatellite alterations at selected tetranucleotides in early-stage colorectal cancers with and without high-frequency microsatellite instability: same, same but different?
Watson, Martin Matthew Christian; Lea, Dordi; Rewcastle, Emma; Hagland, Hanne Røland; Søreide, Kjetil
Journal article
Microsatellite instability (MSI) is associated with better prognosis in colorectal cancer (CRC). Elevated microsatellite alterations at selected tetranucleotides (EMAST) is a less-understood form of MSI. Here, we aim to investigate the role of EMAST in CRC±MSI related to clinical and tumor-specific characteristics. A consecutive, population-based series of stage I–III colorectal cancers were investigated for MSI and EMAST using PCR primers for 10 microsatellite markers. Of 151 patients included, 33 (21.8%) had MSI and 35 (23.2%) were EMAST+, with an overlap of 77% for positivity, (odds ratio [OR] 61; P < 0.001), and 95% for both markers being negative. EMAST was more prevalent in colon versus rectum (86% vs. 14%, P = 0.004). EMAST+ cancers were significantly more frequent in proximal colon (77 vs. 23%, P = 0.004), had advanced t-stage (T3–4 vs. T1–2 in 94% vs. 6%, respectively; P = 0.008), were larger (≥5 cm vs. <5 cm in 63% and 37%, respectively; P = 0.022) and had poorly differentiated tumor grade (71 vs. 29%, P < 0.01). Furthermore, EMAST+ tumors had a higher median number of harvested lymph nodes than EMAST− (11 vs. 9 nodes; P = 0.03). No significant association was found between EMAST status and age, gender, presence of distant metastases or metastatic lymph nodes, and overall survival. A nonsignificant difference toward worse survival in node-negative colon cancers needs confirmation in larger cohorts. EMAST+ cancers overlap and share features with MSI+ in CRC. Overall, survival was not influenced by the presence of EMAST, but may be of importance in subgroups such as node-negative disease of the colon.
2016-07-01T00:00:00ZClinical patterns of presentation and attenuated inflammatory response in octo- and nonagenarians with perforated gastroduodenal ulcershttp://hdl.handle.net/1956/16170
Clinical patterns of presentation and attenuated inflammatory response in octo- and nonagenarians with perforated gastroduodenal ulcers
Søreide, Kjetil; Thorsen, Kenneth; Søreide, Jon Arne
Journal article
<p>Background. Perforated gastrodudenal ulcer (PGDU) is an operative emergency with high mortality rates. The growing elderly populationincreasingly presents with need for geriatric acute operative care. Current knowledge of age-specific characteristics in presentation, diagnosis, and outcome for PGDU in the elderly is scarce.</p>
<p>Methods. We reviewed a consecutive, population-based cohort of patients with PGDU, octa- and nonagenarians were compared with younger patients for variation in patterns of presentation and outcomes. Patterns and outcomes observed included 30-day mortality, serious complications (Clavien-Dindo 3 and 4), and duration of stay.</p>
<p>Results. Of the 244 patients, 127 were women (52%); median age was 68 years; and 59 patients (24.2%) were ≥80 years. Two thirds had gastric ulcers (n = 168; 67.2%). On admission, hemoglobin levels, white blood cell count, and serum levels of C-reactive protein, bilirubin, and albumin differed significantly between the age groups. Diagnosis, treatment, and the occurrence of severe complications did not differ with age. The median hours of delayto definitive treatment did not differ significantly for all ages, but patients $80 years had a greater proportion (44.1% compared with 25.8%) of delay &gt;12 hours (odds ratio 2.26, 95% confidence interval 1.22&ndash;4.17; P = .008). Overall mortality was 38 (15.6%); no deaths occurred in patients &lt;55 years. Over one half of deaths occurred in those ≥80 years (odds ratio 4.76, 2.30&ndash;9.83; P &lt;.001). Duration of hospital stay was significantly greater in elderly survivors, and fewer were discharged within a week.</p>
<p>Conclusion. Octa- and nonagenarians with PGDU present with fewer signs of peritonitis and have an attenuated inflammatory response. The very elderly have twice the risk of long delays to definitive treatment and almost 5 times increased risk of mortality.</p>
2016-08-01T00:00:00ZBrain MR spectroscopy in autism spectrum disorder—the GABA excitatory/inhibitory imbalance theory revisitedhttp://hdl.handle.net/1956/16165
Brain MR spectroscopy in autism spectrum disorder—the GABA excitatory/inhibitory imbalance theory revisited
Brix, Maiken Kirkegaard; Ersland, Lars; Hugdahl, Kenneth; Grüner, Renate; Posserud, Maj-Britt Rocio; Hammar, Åsa; Craig-Craven, Alexander Richard; Noeske, Ralph; Evans, C. John; Walker, Hanne Bjørg Hansen; Midtvedt, Tore; Beyer, Mona K.
Journal article
Magnetic resonance spectroscopy (MRS) from voxels placed in the left anterior cingulate cortex (ACC) was measured from 14 boys with Autism Spectrum Disorder (ASD) and 24 gender and age-matched typically developing (TD) control group. Our main aims were to compare the concentration of γ-aminobutyric acid (GABA) between the two groups, and to investigate the relationship between brain metabolites and autism symptom severity in the ASD group. We did find a significant negative correlation in the ASD group between Autism Spectrum Screening Questionnaire (ASSQ) and GABA+/Cr, which may imply that severity of symptoms in ASD is associated with differences in the level of GABA in the brain, supporting the excitatory/inhibitory (E/I) imbalance theory. However we did not find a significant difference between the two groups in GABA levels.
2015-06-22T00:00:00ZCholine intake and Incidence of Acute Myocardial Infarction in Patients with Stable Angina Pectorishttp://hdl.handle.net/1956/16087
Choline intake and Incidence of Acute Myocardial Infarction in Patients with Stable Angina Pectoris
Palma, Marcela Guimaraes
Master thesis
Introduction: Cardiovascular diseases are the leading cause of death worldwide. It can be
defined as a group of interrelated diseases of the heart and blood vessels, including
atherosclerotic cardiovascular diseases. Acute myocardial infarction (AMI) may be the first
manifestation of coronary heart disease (CHD) or it may develop during more chronic stages
of CHD. The major risk factors for CHD are tobacco use, unhealthy diet, obesity, physical
inactivity, hypertension, diabetes, and hyperlipidemia. Thus, life style changes affecting these
risk factors are important in primary and secondary prevention of CHD.
A high CHD risk diet comprises high intakes of fat, refined sugar, meat and low intake of
fruits and vegetables. The essential nutrient choline, which is the focus of the current study, is
found in virtually all foods, but meat and other animal products are the main sources of
dietary choline among omnivorous populations. These are food items that, in accordance with
current dietary guidelines, should be limited in our diet. Intak of choline has been linked to
increased AMI risk. However, few studies have investigated the association between choline
intake and risk of AMI in patients with established CHD.
Objective: To analyse a possible association between choline intake and risk of AMI in
patients with suspected stable angina pectoris.
Methods: We used data from 2019 patients from the Western Norway B-Vitamin Intervention
Trial who underwent coronary angiography at baseline. Average food consumption for the
previous year was collected via a 169-item food frequency questionnaire at baseline. Total
intakes of choline and choline species were adjusted by total energy intake by using the
residual method. For continuous variables, we used Students T-test to analyze differences
between patients who developed AMI and those who did not, and linear regression to explore
trends across quartiles of total choline intake. For dichotomous and categorical variables
logistic regression and Fisher’s exact test were used, respectvely.
For estimating the risk of AMI, Cox proportional hazards regression models were used.
Hazard ratios and confidence intervals are presented per 100 mg increase in total choline
intake and for each 10 mg increase in free choline, phosphatidylcholine, phosphocholine,
sphingomyelin and glycerophosphocholine. Three models were tested to control for
confounders on the effect of dietary choline on risk of AMI. Finally, potential non-linear
associations between choline intake and risk of AMI were explored using general additive
models.
Results: Mean (SD) daily total choline intake among the 2019 participants was 294 (65.1) mg
(79.7% were men, mean age was 61.8 (9.7) years). No significant association between
choline intake and sex, age, prior CVD or extent of coronary artery disease (CAD) at
baseline. Higher choline intake was however positively associated with several established
CVD risk factors including smoking (p <0.001), BMI (p <0.001), hypertension (p <0.005),
diabetes (p < 0.001), serum glucose (p <0.001), but inversely associated with plasma total
homocysteine (Hcy) (p <0.001). No association was observed with lipid related parameters.
During a median follow up of 7.2 (2.4) years, 297 patients experienced an AMI. In the crude
model, adjusted for total energy intake, the risk of AMI increased with 28% (CI 1.09-1.49)
for each 100 mg increase in choline intake. Model 2 was also adjusted for sex, age, smoking,
previous AMI, previous coronary artery bypass grafting (CABG) and extension of CAD at
baseline. Model 3 was further adjusted for BMI and diabetes. In the multivariate models the
risk was slightly attenuated. Intake of phosphatidylcholine and sphingomyelin was positively
associated with risk of AMI, whereas intake of free choline, phosphocholine and
glycerophosphocholine showed no association with AMI risk.
Conclusion: In patients with SAP, a higher intake of choline is associated with a number of
established risk factors for CVD but with independent excess risk of AMI.
2017-06-22T00:00:00ZAssessment of Nutritional Status in Kidney Transplant Patients at Haukeland University Hospitalhttp://hdl.handle.net/1956/16037
Assessment of Nutritional Status in Kidney Transplant Patients at Haukeland University Hospital
Dahl, Helene
Master thesis
Background and aims: Chronic kidney disease (CKD) may give implications of nutritional status, and studies suggest that patients with CKD have increased risk of malnutrition and nutrition related conditions such as sarcopenia. Not all implications related to kidney disease will disappear after kidney transplantation, and side effects from polypharmacy may give additional implications in these patients. Nutritional status in kidney transplant patients has not been reviewed in many studies. The aim of this study was to assess nutritional status in kidney transplant patients and identify which nutritional challenges are present after kidney transplantation. Methods: A cross-sectional observational study was conducted which included kidney transplant recipients from the outpatients’ clinic at the department of nephrology at HUS September 2016 - January 2017. Information about disease history, lifestyle, health condition, anthropometric measurements, functional measurements, dietary intake, and chemical clinical analysis results were obtained. Results: The study population consisted of 72 patients (71% male) with the median age of 59.5 years (IQR 49.0, 66.8). Mean BMI was 26.7 kg/m2 (SD ± 4.5), with 65% of the study population being overweight or obese. Central obesity was identified in 50% of the study population. Nutritional risk was identified in 7-10% of the patients, depending on which screening tool applied. Sarcopenia was identified in 31% of the study population diagnosed by reduced muscle strength and muscle mass, measured by HGS and BIA, respectively. Conclusion: The nutritional challenges in kidney transplant recipients are presented as overnutrition in term of overweight and obesity rather than undernutrition in this study population. Assessment of body composition and muscle strength revealed a prominent proportion of sarcopenic patients, in all BMI-categories. Results suggest that nutritional care concerning overnutrition and sarcopenia may be necessary in this patient group, and that measurement of weight and height for the calculation of BMI may not be sufficient in assessment of nutritional status and body composition.
2017-06-16T00:00:00ZPre- and postoperative nutritional status and dietary intake in patients undergoing gastroenterological surgery at St. Olavs Hospitalhttp://hdl.handle.net/1956/15980
Pre- and postoperative nutritional status and dietary intake in patients undergoing gastroenterological surgery at St. Olavs Hospital
Ystås, Tonja Ulvenes
Master thesis
Introduction and aim: The prevalence of malnutrition in hospital ranges between 10%-60%.
Patients undergoing gastrointestinal surgery are at risk for malnutrition both because of
insufficient food intake pre- and/or postoperatively and because of stress from surgery with
following increased metabolism. Malnutrition in surgery has been found to be an independent
risk factor affecting the postoperative outcome negatively. Finding suitable, validated and
standardized methods to screen for malnutrition risk is an essential step towards improving
perioperative nutritional status. The aim of this study was to describe nutritional status and diet
before gastroenterological surgery and one month after surgery, and to compare the use of two
nutritional screening tools in predicting postoperative outcome.
Method: This was a prospective observational study recruiting patients from preoperative
outpatient clinic before upper- or lower gastrointestinal surgery. At the outpatient clinic,
patients were screened with the two nutritional screening tools NRS-2002 and PG-SGA.
Postoperative outcomes, such as complications and length of hospital stay, were registered. The
predictive value of nutritional risk (NRS-2002) and malnutrition (PG-SGA) on complications
and LOS was evaluated using univariate and multivariate regression analyses. Dietary intake
was assessed before surgery at the outpatient clinic, and one month after surgery over phone,
using 24 h recall method.
Results: The study recruited 101 surgical patients with a mean BMI of 26±5 kg/m2 and mean
age of 60±17 years. NRS-2002 identified 24 % at nutritional risk and PG-SGA identified 28 %
as malnourished. The impact of nutritional risk (NRS-2002) on the likelihood of postoperative
complications recorded an OR of 2.71 (95% CI: 0.95-7.73; p=0.063) and nutritional status (PGSGA)
recorded an OR of 2.03 (95% CI: 0.73-5.68; p=0.176). The respective adjusted effect recorded an OR of 3.88 (95% CI: 1.07-14.06; p= 0.039) and 3.07 (95% CI: 0.90-10.54; p=0.075), respectively. Neither of the two screening tools contributed significant in predicting length of hospital stay. Overall, mean energy- and protein intake did not differ significant pre- and postoperatively. Patients at risk or malnourished consumed significant less energy and
protein before surgery compared to one-month after surgery.
Conclusion: Two screening tools revealed that nutritional risk and malnutrition are frequent in
patients before gastrointestinal surgery, even in a population with average BMI indicating
overweight. NRS-2002 defining patients at risk presented the strongest predictor of
complications in the adjusted analysis controlling for age, surgery, and co-morbidities.
2017-06-10T00:00:00Z"Everyone Needs a Friend Sometimes" - social predictors of long-term remission in first episode psychosishttp://hdl.handle.net/1956/15951
"Everyone Needs a Friend Sometimes" - social predictors of long-term remission in first episode psychosis
Bjørnestad, Jone Ravndal; Joa, Inge; Larsen, Tor Ketil; Langeveld, Johannes H.; Davidson, Larry; Hegelstad, Wenche; Anda-Ågotnes, Liss Gøril; Veseth, Marius; Melle, Ingrid; Johannessen, Jan Olav; Brønnick, Kolbjørn Selvåg
Journal article
<p>Background: Predictors of long-term symptomatic remission are crucial to the successful tailoring of treatment in first episode psychosis. There is lack of studies distinguishing the predictive effects of different social factors. This prevents a valid evaluating of their independent effects.</p>
<p>Objectives: To test specific social baseline predictors of long-term remission. We hypothesized that first, satisfaction with social relations predicts remission; second, that frequency of social interaction predicts remission; and third, that the effect of friend relationship satisfaction and frequency will be greater than that of family relations satisfaction and frequency.</p>
<p>Material and Methods: A sample of first episode psychosis (n = 186) completed baseline measures of social functioning, as well as clinical assessments. We compared groups of remitted and non-remitted individuals using generalized estimating equations analyses.</p>
<p>Results: Frequency of social interaction with friends was a significant positive predictor of remission over a two-year period. Neither global perceived social satisfaction nor frequency of family interaction showed significant effects.</p>
<p>Conclusions: The study findings are of particular clinical importance since frequency of friendship interaction is a possibly malleable factor. Frequency of interaction could be affected through behavioral modification and therapy already from an early stage in the course, and thus increase remission rates.</p>
2016-10-04T00:00:00ZCytokine Patterns in Tuberculosis Infection; IL-1ra, IL-2 and IP-10 Differentiate Borderline QuantiFERON-TB Samples from Uninfected Controlshttp://hdl.handle.net/1956/15930
Cytokine Patterns in Tuberculosis Infection; IL-1ra, IL-2 and IP-10 Differentiate Borderline QuantiFERON-TB Samples from Uninfected Controls
Wergeland, Ida; Assmus, Jörg; Dyrhol-Riise, Anne Ma
Journal article
<p>Background: Interferon gamma release assays (IGRAs) do not discriminate between active tuberculosis (TB) and latent TB infection (LTBI), which limit their use in TB endemic areas. Subjects with QuantiFERON-TB (QFT) results around the diagnostic cut-off more likely show inconsistent results on serial testing which makes the interpretation of the assay difficult. We have studied potential biomarkers in patients with various stages of TB infection and with borderline QFT tests compared to those with higher values.</p>
<p>Methods: 27 soluble biomarkers were analysed in QFT supernatants from patients with active TB (n = 18), individuals with LTBI (n = 48) and from QFT negative controls (n = 16) by the Multiplex bead assay. The LTBI group was classified into two groups according to QFT IFN-&gamma; levels; QFT borderline (0.35&ndash;0.70 IU/mL, n = 11) or QFT high (&gt;0.70 IU/mL, n = 36).</p>
<p>Results: The levels of IL-1ra, IL-2, IL-13, IL-15, IFN-&gamma;, IP-10 and MCP-1 in background corrected TB antigen stimulated supernatants (TBAg-Nil) significantly distinguished both active TB and LTBI QFT high groups from the QFT negative controls (p&le;0.004). In addition, IL-1ra, IL-2 and IP-10 significantly differentiated the QFT borderline group from the controls (p&le;0.001). Still, in the QFT borderline group the IL-1ra and IP-10 levels were not significant different from neither the QFT high nor the active TB group, whereas the IL-2 levels were lower (p&le;0.003). The level of IP-10 showed the best separation between the QFT borderline group and the QFT negative controls (AUC 0.92) and offered 100% sensitivity for active TB.</p>
<p>Conclusion: IL-1ra, IL-2 and IP-10 differentiate QFT borderline samples from uninfected controls and the majority of QFT borderline subjects were classified as LTBI by these markers. Still, inconsistency was seen, and further studies are needed to examine the performance of alternative markers before concluded if they could be used as diagnostics tools.</p>
2016-09-29T00:00:00ZHigh flow nasal cannula in children: A literature reviewhttp://hdl.handle.net/1956/15920
High flow nasal cannula in children: A literature review
Mikalsen, Ingvild Bruun; Davis, Peter; Øymar, Knut
Journal article
High flow nasal cannula (HFNC) is a relatively new non-invasive ventilation therapy that seems to be well tolerated in children. Recently a marked increase in the use of HFNC has been seen both in paediatric and adult care settings. The aim of this study was to review the current knowledge of HFNC regarding mechanisms of action, safety, clinical effects and tolerance in children beyond the newborn period.
We performed a systematic search of the databases PubMed, Medline, EMBASE and Cochrane up to 12th of May 2016. Twenty-six clinical studies including children on HFNC beyond the newborn period with various respiratory diseases hospitalised in an emergency department, paediatric intensive care unit or general ward were included. Five of these studies were interventional studies and 21 were observational studies. Thirteen studies included only children with bronchiolitis, while the other studies included children with various respiratory conditions. Studies including infants hospitalised in a neonatal ward, or adults over 18 years of age, as well as expert reviews, were not systematically evaluated, but discussed if appropriate.
The available studies suggest that HFNC is a relatively safe, well-tolerated and feasible method for delivering oxygen to children with few adverse events having been reported. Different mechanisms including washout of nasopharyngeal dead space, increased pulmonary compliance and some degree of distending airway pressure may be responsible for the effect. A positive clinical effect on various respiratory parameters has been observed and studies suggest that HFNC may reduce the work of breathing. Studies including children beyond the newborn period have found that HFNC may reduce the need of continuous positive airway pressure (CPAP) and invasive ventilation, but these studies are observational and have a low level of evidence. There are no international guidelines regarding flow rates and the optimal maximal flow for HFNC is not known, but few studies have used a flow rate higher than 10 L/min for infants.
Until more evidence from randomized studies is available, HFNC may be used as a supplementary form of respiratory support in children, but with a critical approach regarding effect and safety, particularly when operated outside of a paediatric intensive care unit.
2016-07-12T00:00:00ZPrimary Leiomyosarcoma of the Pancreas—a Case Report and a Comprehensive Reviewhttp://hdl.handle.net/1956/15893
Primary Leiomyosarcoma of the Pancreas—a Case Report and a Comprehensive Review
Søreide, Jon Arne; Undersrud, Erling Sandøy; Al-Saiddi, Mohammed; Tholfsen, Tore; Søreide, Kjetil
Journal article
<p>Purpose: Primary mesenchymal tumors of the pancreas are rare, with leiomyosarcomas the most encountered entities among the pancreatic sarcomas. With few exceptions, single case reports published over the last six decades constitute the entire scientific literature on this topic. Thus, evidence regarding clinical decision-making is scant.</p>
<p>Methods: Based on a case report and an extensive literature search in PubMed, we discuss the clinical aspects and current management of this rare malignancy.</p>
<p>Results: We identified only two papers with more than a single case presentation; these institutional patient series were limited to five and nine patients. Additionally, a few papers sought to summarize the individual case reports published in the English and/or Chinese language. The clinical presentation is rather non-specific. Moreover, modern imaging modalities are insufficiently accurate to diagnose leiomyosarcoma of the pancreas. Treatment goals include a complete resection with free margins. Proper morphologic examination using immunohistochemistry and the application of a grading system are clinically important for prognostication. The efficacy of adjuvant treatments has not been established.</p>
<p>Conclusion: Primary pancreatic leiomyosarcoma is extremely rare, and the scientific literature is primarily based on single case reports. Conclusions on management and prognosis should be drawn with caution. A multidisciplinary team consultation is warranted to discuss a thorough individual treatment plan based on the available scientific literature, despite its low evidence level.</p>
2016-12-01T00:00:00ZIntegrin a11 is overexpressed by tumour stroma of head and neck squamous cell carcinoma and correlates positively with alpha smooth muscle actin expressionhttp://hdl.handle.net/1956/15889
Integrin a11 is overexpressed by tumour stroma of head and neck squamous cell carcinoma and correlates positively with alpha smooth muscle actin expression
Parajuli, Himalaya; Teh, Muy-Teck; Abrahamsen, Siren; Christoffersen, Ingeborg Monge; Neppelberg, Evelyn; Lybak, Stein; Osman, Tarig Al-Hadi; Johannessen, Anne Christine; Gullberg, Donald; Skarstein, Kathrine; Costea, Daniela Elena
Journal article
<p>BACKGROUND: Cancer-associated fibroblasts (CAFs) were shown to be important for tumour progression in head and neck squamous cell carcinomas (HNSCCs). Their heterogeneity and lack of specific markers is increasingly recognized. Integrin a11 was recently shown to be expressed by CAFs and might serve as a specific CAF marker.</p>
<p>AIM: To investigate integrin a11 expression and its correlation with the expression of a well-known marker of CAF, alpha smooth muscle actin (a-SMA), in HNSCC.</p>
<p>METHODS: Fresh frozen (FF) and formalin-fixed paraf- fin-embedded (FFPE) samples from healthy volunteers (n = 24), oral lichen planus (OLP) (n = 32) and HNSCC (n = 106) were collected together with clinical data after ethical approval. Immunohistochemistry to detect integrin a11 and a-SMA was performed on FF and FFPE samples. qPCR for integrin a11 (ITGA11) and a-SMA (ACTA2) was performed on FF samples. Data were analysed using chi-square test and Kaplan&ndash;Meier survival analysis.</p>
<p>RESULTS: Significantly higher levels of integrin a11 and a-SMA at both protein and mRNA levels were found in HNSCC vs. normal controls and OLP. A strong correlation was found between integrin a11 and a-SMA expression, and double staining showed their colocalization. Both integrin a11 and a-SMA were detected surrounding metastatic islands. Expression of a-SMA at tumour front but not tumour centre correlated with patient survival.</p>
<p>CONCLUSION: Integrin a11 was overexpressed in HNSCC stroma and colocalized with a-SMA. Expression of a-SMA at tumour front but not tumour centre had prognostic value for survival, pinpointing the importance of assessing tumour front when eva</p>
2017-04-01T00:00:00ZThe effect of low FODMAP diet in patients with radiation-induced small bowel diseasehttp://hdl.handle.net/1956/15874
The effect of low FODMAP diet in patients with radiation-induced small bowel disease
Larsen, Trine
Master thesis
Rationale: Patients suffering from chronic radiation-induced small bowel disease (RISBD) after cancer treatment have similar symptoms as patients with IBS (irritable bowel syndrome), despite dissimilar pathological origin. The low FODMAP (fermentable oligo-, di-, monosaccharides and polyols) diet (LFD) is a widespread management strategy for IBS. The aim of the conducted study was to investigate the effects of LFD on symptoms and health related quality of life (HRQOL) for patients with chronic RISBD. Methods: In an open pilot study, 11 patients with RISBD related IBS symptoms were instructed to follow LFD throughout a 4-week intervention period. IBS Severity Scoring System (IBS-SSS) and IBS Symptom Questionnaire (IBS-SQ) were used to assess symptoms. An Ad hoc questionnaire measured grade of damage and typical RISBD complaints. Short Form Nepean Dyspepsia Index (SF-NDI) and 12-item Short Form Health Survey (SF-12) were used to evaluate HRQOL. A 3-day food record was used to estimate baseline intake of FODMAPs, to reveal dietary changes and to assess adherence to the diet. All schemes were completed at baseline and at 4 weeks. Results: FODMAP intake was successfully reduced, and main additional changes in the diet were reduced intake of energy, carbohydrates and fiber. The adherence to the diet was high (mean 94.8%). IBS symptoms improved significantly based on mean total score of IBS-SSS and IBS-SQ, which changed from 310.2±60.7 to 171.4±107.2 (p=0.001) and 27.4±4.1 to 15.7±10.1 (p=0.002), respectively. The severity of abdominal pain, abdominal distension, belching/flatulence, constipation, diarrhea, early satiety, dissatisfaction with bowel habits and interference with life in general, improved significantly. Tendencies of improvement were also measured in comorbidity complaints and typical RISBD complaints. HRQOL improved based on SF-NDI total score, which changed from 30.5±9.4 to 18.3±8.2 (p=0.001) and based on mental (p=0.047) and physical (p=0.134) component summary score of SF-12. Conclusions: The low FODMAP diet seems effective in alleviating IBS symptoms, and improving HRQOL in patients with RISBD. High compliance to LFD is possible with adequate diet counseling and continuous guidance. Further controlled studies with larger sample size should be conducted to verify our results and hopefully enable the implementation of LFD as a future management strategy for chronic RISBD.
2017-05-09T00:00:00ZPNKP Mutations Identified by Whole-Exome Sequencing in a Norwegian Patient with Sporadic Ataxia and Edemahttp://hdl.handle.net/1956/15792
PNKP Mutations Identified by Whole-Exome Sequencing in a Norwegian Patient with Sporadic Ataxia and Edema
Tzoulis, Charalampos; Sztromwasser, Pawel Szymon; Johansson, Stefan; Gjerde, Ivar Otto; Knappskog, Per; Bindoff, Laurence
Journal article
We identified PNKP mutations in a Norwegian woman with AOA. This patient had the typical findings with cognitive dysfunction, peripheral neuropathy, cerebellar dysarthria, horizontal nystagmus, oculomotor apraxia, and severe truncal and appendicular ataxia. In addition, she had hypoalbuminemia and massive lower limb edema which showed some improvement with treatment. Exome sequencing identified two heterozygous mutations, one in exon 14 (c.1196T>C, p.Leu399Pro) and one in exon 16 (c.1393_1396del, p.Glu465*). This is the first non-Portuguese patient with AOA due to PNKP mutations and provides independent verification that PNKP mutations cause AOA.
2017-02-01T00:00:00ZCombined variants in reading epilepsy; coexisting anterior and posterior variants camouflaged as heat cramps where the patient finds his own diagnosis searching the internethttp://hdl.handle.net/1956/15791
Combined variants in reading epilepsy; coexisting anterior and posterior variants camouflaged as heat cramps where the patient finds his own diagnosis searching the internet
Olberg, Henning Kristian; Eichele, Tom; Schwarzlmüller, Thomas; Lind, Jonas; Hjelland, Ina Elen; Engelsen, Bernt Andreas
Journal article
Reading epilepsy is a form of reflex-induced seizures. Two entities are postulated as part of a clinical spectrum; one anterior variant with jaw jerks and orofacial myoclonia and another posterior variant with visual symptoms and alexia or dyslexia. We present a case with suggestible evidence of both conditions coexisting within the same patient, a finding that, to our knowledge, has not been previously reported. The diagnosis in this specific case was contributed to by the patient searching the internet.
2016-01-01T00:00:00ZPost resuscitation care – some words of caution and a call for actionhttp://hdl.handle.net/1956/15790
Post resuscitation care – some words of caution and a call for action
Søreide, Eldar; Larsen, Alf Inge
Journal article
This fall the European Resuscitation Council (ERC) and the European Cardiology Society (ESC) publish updated post resuscitation care guidelines. For these guidelines to have an impact they must be implemented into daily clinical practice. Newer studies imply that differences in hospital care explain much of the observed differences in survival after out-of-hospital cardiac arrest. A recent Nordic (Denmark, Finland, Iceland, Norway, Sweden) survey suggests worrisome variations in post resuscitation care provided and should urge us all to act in the coming years. One important step will be to build up resuscitation systems with integrated cardiac arrest centres in all the 5 Nordic countries and benchmark process of care, financial implications and survival.
2015-11-04T00:00:00ZResection of asymptomatic primary tumour in unresectable stage IV colorectal cancer: time to move on from propensity matched scores to randomized controlled trialshttp://hdl.handle.net/1956/15788
Resection of asymptomatic primary tumour in unresectable stage IV colorectal cancer: time to move on from propensity matched scores to randomized controlled trials
Søreide, Kjetil
Journal article
2016-11-01T00:00:00ZNo association of tobacco use and disease activity in multiple sclerosishttp://hdl.handle.net/1956/15743
No association of tobacco use and disease activity in multiple sclerosis
Kvistad, Silje; Myhr, Kjell-Morten; Holmøy, Trygve; Saltyte Benth, Jurate; Løken-Amsrud, Kristin Ingeleiv; Wergeland, Stig; Beiske, Antonie Giæver; Bjerve, Kristian S; Hovdal, Harald Olav; Lilleås, Finn; Midgard, Rune; Pedersen, Tom; Bakke, Søren Jacob; Torkildsen, Øivind
Journal article
<p>Objective: To study whether tobacco use is associated with MRI and clinical disease activity in patients with multiple sclerosis (MS).</p>
<p>Methods: Prospective cohort study of 87 patients with relapsing-remitting MS originally included in a randomized placebo-controlled trial of omega-3 fatty acids in MS (the OFAMS Study). Serum levels of cotinine (biomarker of tobacco use) were analyzed at baseline and every 6 months for 2 years. MRI activity was assessed at baseline and monthly for 9 months and after 12 and 24 months.</p>
<p>Results: Fifty-three patients (61%) had serum cotinine levels &ge;85 nmol/L on &ge;60% of the measurements and were considered tobacco users and 34 (39%) had cotinine levels &lt;85 nmol/L, consistent with non&ndash;tobacco use. There was no association between tobacco use and the occurrence of new gadolinium-enhancing T1 lesions, new or enlarging T2 lesions, or their aggregate (combined unique activity). Furthermore, there was no association between cotinine levels and MRI activity for the tobacco users, and tobacco users did not have more relapses or Expanded Disability Status Scale progression.</p>
<p>Conclusion: Our results indicate that tobacco use does not directly influence MRI activity or relapse rate in MS. This may implicate that the reported association between smoking and MS disease progression could be mediated through other mechanisms.</p>
2016-08-01T00:00:00ZEffect of Perioperative Dexamethasone and Different NSAIDs on Anastomotic Leak Risk: A Propensity Score Analysishttp://hdl.handle.net/1956/15732
Effect of Perioperative Dexamethasone and Different NSAIDs on Anastomotic Leak Risk: A Propensity Score Analysis
Rushfeldt, Christian; Agledahl, Uwe; Sveinbjørnsson, Baldur; Søreide, Kjetil; Wilsgaard, Tom
Journal article
<p>Background: Perioperative use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with risk of anastomotic leak (AL). However, concomitant use of other drugs could infer a bias in risk assessment. Thus, we aimed to interrogate the risk of AL associated with NSAIDs and steroids used perioperatively.</p>
<p>Methods: This study includes a consecutive series of patients having surgery involving an intestinal anastomosis from Jan 2007 to Dec 2009. Data records included demographic, perioperative, and surgical characteristics; AL rates; and use of NSAIDs and steroids. Risk of leak were estimated using unadjusted and multivariable (propensity score)-adjusted logistic regression models and reported as odds ratios (ORs).</p>
<p>Results: A total of 376 patients underwent 428 operations of which 67 (15.7 %) had AL. With no medication receivers as reference, the OR for leak when adjusted for age, sex, and propensity score was 1.07 (p = 0.92) for ketorolac, 1.63 (p = 0.31) for diclofenac and 0.41 (p = 0.19) for dexamethasone. Risk was increased for malignancy (OR 1.88, p = 0.023), use of a vasopressor (OR 2.52, p = 0.007), blood transfusions (OR 1.93, p = 0.026), and regular use of steroids (OR 7.57, p = 0.009).</p>
<p>Conclusions: Other factors than perioperative drugs are crucial for risk of AL. Perioperative dexamethasone was associated with a nonsignificant reduced risk of AL.</p>
2016-11-01T00:00:00ZRisk factors and preventive strategies for post-operative pancreatic fistula after pancreatic surgery: a comprehensive reviewhttp://hdl.handle.net/1956/15669
Risk factors and preventive strategies for post-operative pancreatic fistula after pancreatic surgery: a comprehensive review
Søreide, Kjetil; Labori, Knut Jørgen
Journal article
<strong>Background:</strong> <p>Pancreas surgery has developed into a fairly safe procedure in terms of mortality, but is still hampered by considerable morbidity. Among the most frequent and dreaded complications are the development of a post-operative pancreatic fistula (POPF). The prediction and prevention of POPF remains an area of debate with several questions yet to be firmly addressed with solid answers.</p>
<strong>Methods:</strong><p> A systematic review of systematic reviews/meta-analyses and randomized trials in the English literature (PubMed/MEDLINE, Cochrane library, EMBASE) covering January 2005 to December 2015 on risk factors and preventive strategies for POPF.</p>
<strong>Results:</strong><p> A total of 49 systematic reviews and meta-analyses over the past decade discussed patient, surgeon, pancreatic disease and intraoperative related factors of POPF. Non-modifiable factors (age, BMI, comorbidity) and pathology (histotype, gland texture, duct size) that indicates surgery are associated with POPF risk. Consideration of anastomotic technique and use of somatostatin-analogs may slightly modify the risk of fistula. Sealant products appear to have no effect. Perioperative bleeding and transfusion enhance risk, but is modifiable by focus on technique and training. Drains may not prevent fistulae, but may help in early detection. Early drain-amylase may aid in detection. Predictive scores lack uniform validation, but may have a role in patient information if reliable pre-operative risk factors can be obtained.</p>
<strong>Conclusions:</strong><p> Development of POPF occurs through several demonstrated risk factors. Anastomotic technique and use of somatostatin-analogs may slightly decrease risk. Drains may aid in early detection of leaks, but do not prevent POPF.</p>
2016-03-01T00:00:00ZTranscriptome sequencing (RNAseq) enables utilization of formalin-fixed, paraffin-embedded biopsies with clear cell renal cell carcinoma for exploration of disease biology and biomarker developmenthttp://hdl.handle.net/1956/15632
Transcriptome sequencing (RNAseq) enables utilization of formalin-fixed, paraffin-embedded biopsies with clear cell renal cell carcinoma for exploration of disease biology and biomarker development
Eikrem, Øystein Solberg; Beisland, Christian; Hjelle, Karin Margrethe; Flatberg, Arnar; Scherer, Andreas; Landolt, Lea Zoe; Skogstrand, Trude; Leh, Sabine Maria; Beisvag, Vidar; Marti, Hans-Peter
Journal article
Formalin-fixed, paraffin-embedded (FFPE) tissues are an underused resource for molecular analyses. This proof of concept study aimed to compare RNAseq results from FFPE biopsies with the corresponding RNAlater® (Qiagen, Germany) stored samples from clear cell renal cell carcinoma (ccRCC) patients to investigate feasibility of RNAseq in archival tissue. From each of 16 patients undergoing partial or full nephrectomy, four core biopsies, such as two specimens with ccRCC and two specimens of adjacent normal tissue, were obtained with a 16g needle. One normal and one ccRCC tissue specimen per patient was stored either in FFPE or RNAlater®. RNA sequencing libraries were generated applying the new Illumina TruSeq® Access library preparation protocol. Comparative analysis was done using voom/Limma R-package. The analysis of the FFPE and RNAlater® datasets yielded similar numbers of detected genes, differentially expressed transcripts and affected pathways. The FFPE and RNAlater datasets shared 80% (n = 1106) differentially expressed genes. The average expression and the log2 fold changes of these transcripts correlated with R2 = 0.97, and R2 = 0.96, respectively. Among transcripts with the highest fold changes in both datasets were carbonic anhydrase 9 (CA9), neuronal pentraxin-2 (NPTX2) and uromodulin (UMOD) that were confirmed by immunohistochemistry. IPA revealed the presence of gene signatures of cancer and nephrotoxicity, renal damage and immune response. To simulate the feasibility of clinical biomarker studies with FFPE samples, a classifier model was developed for the FFPE dataset: expression data for CA9 alone had an accuracy, specificity and sensitivity of 94%, respectively, and achieved similar performance in the RNAlater dataset. Transforming growth factor-ß1 (TGFB1)-regulated genes, epithelial to mesenchymal transition (EMT) and NOTCH signaling cascade may support novel therapeutic strategies. In conclusion, in this proof of concept study, RNAseq data obtained from FFPE kidney biopsies are comparable to data obtained from fresh stored material, thereby expanding the utility of archival tissue specimens.
2016-02-22T00:00:00ZAutomated spectrophotometric bicarbonate analysis in duodenal juice compared to the back titration methodhttp://hdl.handle.net/1956/15631
Automated spectrophotometric bicarbonate analysis in duodenal juice compared to the back titration method
Erchinger, Friedemann Georg; Engjom, Trond; Gudbrandsen, Oddrun Anita; Tjora, Erling; Gilja, Odd Helge; Dimcevski, Georg Gjorgji
Journal article
<strong>Objectives</strong>
<p>We have recently evaluated a short endoscopic secretin test for exocrine pancreatic function. Bicarbonate concentration in duodenal juice is an important parameter in this test. Measurement of bicarbonate by back titration as the gold standard method is time consuming, expensive and technically difficult, thus a simplified method is warranted. We aimed to evaluate an automated spectrophotometric method in samples spanning the effective range of bicarbonate concentrations in duodenal juice. We also evaluated if freezing of samples before analyses would affect its results.</p>
<strong>Methods</strong>
<p>Patients routinely examined with short endoscopic secretin test suspected to have decreased pancreatic function of various reasons were included. Bicarbonate in duodenal juice was quantified by back titration and automatic spectrophotometry. Both fresh and thawed samples were analysed spectrophotometrically.</p>
<strong>Results</strong>
<p>177 samples from 71 patients were analysed. Correlation coefficient of all measurements was r = 0.98 (p &lt; 0.001). Correlation coefficient of fresh versus frozen samples conducted with automatic spectrophotometry (n = 25): r = 0.96 (p &lt; 0.001)</p>
<strong>Conclusions</strong>
<p>The measurement of bicarbonate in fresh and thawed samples by automatic spectrophotometrical analysis correlates excellent with the back titration gold standard. This is a major simplification of direct pancreas function testing, and allows a wider distribution of bicarbonate testing in duodenal juice. Extreme values for Bicarbonate concentration achieved by the autoanalyser method have to be interpreted with caution.</p>
2016-02-03T00:00:00ZThe MDM4 SNP34091 (rs4245739) C-allele is associated with increased risk of ovarian—but not endometrial cancerhttp://hdl.handle.net/1956/15623
The MDM4 SNP34091 (rs4245739) C-allele is associated with increased risk of ovarian—but not endometrial cancer
Gansmo, Liv Beathe; Bjørnslett, Merete Pauline; Halle, Mari Kyllesø; Salvesen, Helga Birgitte; Dørum, Anne; Birkeland, Einar Elvbakken; Hveem, Kristian; Romundstad, Pål Richard; Vatten, Lars Johan; Lønning, Per Eystein; Knappskog, Stian
Journal article
The MDM4 protein (also known as MDMX or HDMX) is a negative regulator of p53, not only by direct interaction but also through its interaction with MDM2. Further, MDM4 overexpression and amplification have been observed in several cancer forms. Recently, a single nucleotide polymorphism (SNP) in the 3’ untranslated region of the MDM4 gene, SNP34091A > C (rs4245739) was reported to alter MDM4 messenger RNA (mRNA) stability by modulating a microRNA binding site, thereby leading to decreased MDM4 levels. In this case-control study, we aimed to evaluate the possible association between MDM4 SNP34091 status and cancer risk by comparing the genotype frequencies in large hospital-based cohorts of endometrial- (n = 1404) and ovarian (n = 1385) cancer patients with healthy female controls (n = 1870). Genotype frequencies were compared by odds ratio (OR) estimates and Fisher exact tests. We found that individuals harboring the MDM4 SNP34091AC/CC genotypes had a significantly elevated risk for serous ovarian cancer (SOC) in general and high-grade serous ovarian cancer (HGSOC) in particular (SOC: OR = 1.18., 95 % CI = 1.01–1.39; HGSOC: OR = 1.25, CI = 1.02–1.53). No association between SNP34091 genotypes and endometrial cancer risk was observed. Our data indicate the MDM4 SNP34091AC/CC genotypes to be associated with an elevated risk for SOC and in particular the HGSOC type.
2016-02-11T00:00:00ZImplementing medical abortion with mifepristone and misoprostol in Norway 1998-2013http://hdl.handle.net/1956/15617
Implementing medical abortion with mifepristone and misoprostol in Norway 1998-2013
Løkeland, Mette; Bjørge, Tone; Iversen, Ole-Erik; Akerkar, Rupali; Bjørge, Line
Journal article
<p>Background: Medical abortion with mifepristone and misoprostol was introduced in Norway in 1998, and since then there has been an almost complete change from predominantly surgical to medical abortions. We aimed to describe the medical abortion implementation process, and to compare characteristics of women obtaining medical and surgical abortion.</p>
<p>Methods: Information from all departments of obstetrics and gynaecology in Norway on the time of implementation of medical abortion and abortion procedures in use up to 12 weeks of gestation was assessed by surveys in 2008 and 2012. We also analysed data from the National Abortion Registry comprising 223 692 women requesting abortion up to 12 weeks of gestation during 1998–2013.</p>
<p>Results: In 2012, all hospitals offered medical abortion, 84.4% offered medical abortion at 9–12 weeks of gestation and 92.1% offered home administration of misoprostol. The use of medical abortion increased from 5.9% of all abortions in 1998 to 82.1% in 2013. Compared with women having a surgical abortion, women obtaining medical abortion had higher odds for undergoing an abortion at 4–6 weeks (adjusted OR 2.33; 95% confidence interval 2.28-2.38). Waiting time between registered request for an abortion until termination was reduced from 11.3 days in 1998 to 7.3 days in 2013.</p>
<p>Conclusions: Norwegian women have gained access to more treatment modalities and simplified protocols for medical abortion. At the same time they obtained abortions at an earlier gestational age and the waiting time has been reduced.</p>
2017-01-01T00:00:00ZEthical challenges, decision-making and end-of-life care in nursing homeshttp://hdl.handle.net/1956/15598
Ethical challenges, decision-making and end-of-life care in nursing homes
Bollig, Georg
Doctoral thesis
<p>Background: Many nursing home residents suffer from multimorbidity, frailty and dementia. A number of ethical challenges are connected to living and dying in nursing homes.</p>
<p>Objective/purpose: This thesis investigates ethical challenges, decision-making and end-oflife care in nursing homes. The research focuses on the views of residents, relatives and staff on these topics.</p>
<p>Materials and methods: The studies relied on a mixed methods approach. Qualitative research was based on qualitative description and interpretive description. In-depth interviews with nursing home residents and focus group interviews with relatives and nursing home staff were conducted. Questionnaires were used to collect data on ethical challenges in nursing homes and to document ethics discussions in five institutions in Austria, Germany and Norway.</p>
<p>Results: From the perspective of residents and relatives, ethical challenges in nursing homes are mostly connected to everyday ethical issues. Residents trust relatives, physicians and nurses to make important decisions on their behalf, but many relatives do not know the resident&rsquo;s wishes, and experience decision making as a burden. Many staff members describe ethical challenges as a burden and appreciate systematic ethics work. The most frequent ethical challenges are lack of resources, end-of-life issues, advance care planning and coercion. Ethics meetings can help to reach consensus in over three-quarters of cases. To implement systematic ethics work in nursing homes, time for reflection, ethics education and support from the management are needed. Residents were entirely absent in the documented ethics meetings.</p>
<p>Conclusion and consequences: Both end-of-life issues and everyday ethical challenges are important in nursing homes. As relatives are often insecure about the wishes of residents, preparatory conversations about treatment preferences and advance care planning should be offered. Systematic ethics work should be implemented in all nursing homes. The regular participation of relatives, physicians and residents in ethics discussions should be encouraged. The participation of residents may strengthen their feelings of autonomy and dignity.</p>
<p>Future perspectives: Further research should aim to investigate strategies to improve the participation of residents in ethics discussions. Research into the views of residents with cognitive impairment is lacking, due to methodological and ethical barriers. The advantages and disadvantages of different models for systematic ethics work in nursing homes need to be explored in more detail.</p>
2017-02-13T00:00:00ZA European multicenter study on systematic ethics work in nursing homeshttp://hdl.handle.net/1956/15597
A European multicenter study on systematic ethics work in nursing homes
Bollig, Georg; Rosland, Jan Henrik; Gjengedal, Eva; Schmidt, Gerda; May, Arnd T.; Heller, Andreas
Journal article
<p>Background: There are many existing ethical challenges in nursing homes. Although different methods and approaches to discussing the ethical challenges have been established, systematic ethics work is not yet a standard in all nursing homes. The aim of the present study was to explore ethical challenges and approaches to implementing systematic ethics work in nursing homes.</p>
<p>Methods: Data from five institutions in Austria, Germany and Norway were collected, and a mixed-methods twotiered study approach was chosen. Documentation of ethics discussions was combined with qualitative focus group interviews with staff members regarding the implementation of systematic ethics work in nursing homes.</p>
<p>Results: One hundred and five ethics meetings were documented. The main topics were advance care planning, ethical challenges associated with artificial nutrition, hospitalisation and end-of-life decision-making. Of the meetings, 33% focused mainly on everyday ethical challenges. In 76% of prospective case discussions, agreements about a solution were reached; however, in 29% of these no residents or relatives participated. The advantages of systematic ethics work described by the staff were enhanced openness and dialogue, overall, and a greater ethical awareness. Many voiced a need for structure and support from the administration.</p>
<p>Conclusions: Systematic ethics work is greatly appreciated by the staff and helps to reach a consensus in the majority of case discussions. It should be implemented in all nursing homes. Attention to everyday ethical challenges is important. The participation of relatives and physicians could be improved. The participation of the residents&rsquo; in ethics discussions should be encouraged to strengthen their autonomy and dignity.</p>
2016-01-01T00:00:00ZPhysical models for simulation and reconstruction of human tissue deformation fields in dynamic MRIhttp://hdl.handle.net/1956/15592
Physical models for simulation and reconstruction of human tissue deformation fields in dynamic MRI
Hodneland, Erlend; Hanson, Erik Andreas; Munthe-Kaas, Antonella Z.; Lundervold, Arvid; Nordbotten, Jan Martin
Journal article
Objective: Medical image registration can be formulated as a tissue deformation problem, where parameter estimation methods are used to obtain the inverse deformation. However, there is limited knowledge about the ability to recover an unknown deformation. The main objective of this study is to estimate the quality of a restored deformation field obtained from image registration of dynamic MR sequences. Methods: We investigate the behavior of forward deformation models of various complexities. Further, we study the accuracy of restored inverse deformations generated by image registration. Results: We found that the choice of 1) heterogeneous tissue parameters and 2) a poroelastic (instead of elastic) model had significant impact on the forward deformation. In the image registration problem, both 1) and 2) were found not to be significant. Here, the presence of image features were dominating the performance. We also found that existing algorithms will align images with high precision while at the same time obtain a deformation field with a relative error of 40%. Conclusion: Image registration can only moderately well restore the true deformation field. Still, estimation of volume changes instead of deformation fields can be fairly accurate and may represent a proxy for variations in tissue characteristics. Volume changes remain essentially unchanged under choice of discretization and the prevalence of pronounced image features. Significance: We suggest that image registration of high-contrast MR images has potential to be used as a tool to produce imaging biomarkers sensitive to pathology affecting tissue stiffness.
2016-10-01T00:00:00ZRevision Knee Arthroplasty in Norway 1994-2011. A register-based study with focus on implant survival, causes and risk of re-revision, pain relief, functional outcome, patient satisfaction, and health related quality of lifehttp://hdl.handle.net/1956/15574
Revision Knee Arthroplasty in Norway 1994-2011. A register-based study with focus on implant survival, causes and risk of re-revision, pain relief, functional outcome, patient satisfaction, and health related quality of life
Leta, Tesfaye Hordofa
Doctoral thesis
<p>Background and purpose: Globally, the number of both primary and revision
knee arthroplasty surgeries performed each year is increasing. Revision knee arthroplasty
surgery is more expensive, technically more difficult and complicated, and consumes
more time and supplies than the primary knee arthroplasty surgery. Consequently,
a reduced number of revisions would mean significant cost saving for society as
well as reduced risk of pain, loss of function, and risk of complications for the patients.
The overall aim of this thesis was to evaluate the outcomes of aseptic revision knee
arthroplasties in Norway in terms of implant survival rate, causes and risk of rerevision,
pain relief, functional outcome, patient satisfaction, and health related quality
of life (HRQOL).</p>
<p>Materials and Methods: All studies included in this thesis were based on aseptic
revision knee arthroplasties reported to the Norwegian Arthroplasty Register
(NAR) in the period 1994-2011 (Paper I-III) and additional information on patient reported
outcomes (PROs) data in the period 1994-2005 (Paper II and III). The PROs
data were on HRQOL (using EQ-5D), functional outcome, pain, and knee related quality
of life (using the Knee Injury and Osteoarthritis Outcome Score (KOOS)), postoperative
pain and satisfaction (using Visual Analogue Scale (VAS)), and on musculoskeletal
comorbidity (using Charnley Category A, B, C). Kaplan-Meier and Coxregression
were used to analyze prostheses survival rate and the risk of re-revision,
whereas t-test and multiple linear regression were used to evaluate mean differences in
the patient reported outcome measures (PROMs) scores between different revision
procedures or treatment groups.</p>
<p>Results: Paper I was based on 1016 primary Total Knee Arthroplasties (TKAs)
revised to TKAs (rev-TKAs). The 10 years survival percentage was 78 %. Deep infection
(28 %) and instability (26 %) were found to be the two most frequent causes of rerevision.
Rev-TKAs with an exchange of the femoral or tibial component exclusively
had a higher risk of re-revision (Relative Risk (RR) =1.7; p=0.02) compared to those
with an exchange of the whole prosthesis. The risk of re-revision was double for men
as compared to women (RR=2.0; p&lt;0.001), and also increased for patients aged &lt; 60
years compared to patients aged &gt;70 years (RR=1.6; p=0.03). The use of bone impaction grafting had a positive effect on the survival rate whereas the use of long stem
extensions, stabilization, bone cement, and patella resurfacing had no significant effect
on the risk of re-revision. Survival rates were similar among prosthesis brands.</p>
<p>In Paper II, the survival rate of TKAs revised with isolated secondary patella resurfacing
(SPR) was assessed based on 308 knees (301 patients) of which 114 patient
had PRO data. The 10 years survival of these revisions was 87 %. Pain alone (10
knees) was the most frequent cause of re-revision. The risk of re-revision was nearly 9
times higher for patients aged &lt;60 years compared to patients aged &gt;70 years
(RR=8.6; p&lt;0.001). The mean EQ-5D index score had significantly improved by 0.15
points following the revision TKA with isolated SPR. Nearly 70 % of patients who
had preoperative severe pain in the EQ-5D pain/discomfort domain reported an improvement
postoperatively. Overall, 63 % of patients that had reported PROs were
satisfied with the SPR procedure. Males had a better result in mean ΔEQ-5D index
score (i.e. postoperative minus preoperative EQ-5D index score). Older patients (&gt;70
years) had better mean scores in the KOOS subscales compared to younger patients (≤
70 years). Patients with unilateral knee joint problem (Charnley category ‘A’) had significantly
better mean score in the KOOS subscales than patients with bilateral or multiple
joint or general health problems.</p>
<p>In Paper III, the survival rates of Unicompartmental Knee Arthroplasties (UKAs)
to TKA (rev-UKAs) vs rev-TKA were assessed based on 768 rev-TKAs and 578 rev-
UKAs, and clinical outcome was assessed based on PROs data from 150 of the 768
rev-TKAs and 127 of the 578 rev-UKAs. The technical difficulty of the surgical procedure
for these two revision groups were assessed as a proxies of the length of operative
time, and the need for bone impaction grafting, stem extensions, and/ or stabilization.
The 10 years survival percentage of rev-UKAs vs rev-TKAs was 82 vs 81 %, respectively.
The overall risk of a re-revision for rev-UKAs vs rev-TKAs was similar
(RR= 1.3; p=0.2), nor did we find any differences in the mean PROM scores. For the
elderly (&gt; 70 years), however, the risk of a re-revision was double for rev-TKAs compared
to the rev-UKAs (RR= 2.1; p=0.05). Loose tibia (28 vs 17 %), pain alone (21 vs
12 %), instability (19 vs 19 %), and deep infection (16 vs 31 %) were main causes of
re-revision for rev-UKAs vs rev-TKAs, respectively. The observed differences in the proportion of reasons for re-revision were statistically significant only for the deep
infection where the rev-TKAs were 2.2 times more frequently re-revised due to deep
infection than the rev-UKAs (RR=2.2; p=0.03). The surgical procedure for rev-TKAs
took longer time (mean=150 vs 114 minutes) and needed more stems (58 vs 19 %),
bone impaction (24 vs 19 %), and stabilizing (27 vs 9 %) compared to rev-UKAs.</p>
<p>Conclusions: The overall conclusion of this PhD study is that the long-term implant
survival following aseptic revision knee arthroplasty in Norway in the period
between 1994 and 2011 was satisfactory (range 78-87 % at 10 years), and a number of
points were noted. Specifically:
<ul>
i) Complete TKA revisions had better implant survival rate than partial revisions.
Thus, partial revisions should only be done after careful consideration in specific
instances. Male gender and younger age (&lt;60 years) were risk factors for rerevision.
Patellar resurfacing, prosthesis brands, constrained implants, the use of stem
extensions, and/or fixation method had no effect on the survival of rev-TKAs, whereas
cases with bone impaction grafting had better results in terms of survival. Deep infection
and instability were the most frequent causes of failure of rev-TKAs (Paper I).</ul>
<ul>
ii) For isolated SPR procedures pain and loosening were the main causes for
re-revision. Young age (&lt;60 years) was a risk factor for re-revision after these procedures.
The mean HRQOL significantly improved following SPR. Isolated SPR procedure
can provide a solution to patients with severe preoperative pain. Still, more than
one-third of patients were dissatisfied with the outcomes of the SPR procedure. Male
patients had a better post-revision improvement in mean EQ-5D index score, and patients
with a unilateral joint problem (Charnley category ‘A’) had significantly better
mean score in KOOS subscales than the other categories following revision TKA with
isolated SPR (Paper II).</ul>
<ul>
iii) The overall outcomes of rev-UKAs and rev-TKAs in terms of implant survival
rates, functional outcome, level of postoperative pain, patient satisfaction, and
change on HRQOL status were similar. However, rev-TKAs seemed to be a technically
more difficult surgical procedure, were re-revised more frequently due to deep infection,
and had a double risk of re-revision for patient older than 70 years compared
to that of rev-UKAs (Paper III).</ul>
</p>
2017-03-10T00:00:00ZExpression of Heat Shock Protein 27 in Melanoma Metastases Is Associated with Overall Response to Bevacizumab Monotherapy: Analyses of Predictive Markers in a Clinical Phase II Studyhttp://hdl.handle.net/1956/15573
Expression of Heat Shock Protein 27 in Melanoma Metastases Is Associated with Overall Response to Bevacizumab Monotherapy: Analyses of Predictive Markers in a Clinical Phase II Study
Schuster, Cornelia; Akslen, Lars A.; Straume, Oddbjørn
Journal article
The aim of this study was to identify potential predictive biomarkers in 35 patients with metastatic melanoma treated with anti-angiogenic bevacizumab monotherapy in a clinical phase II study. The immunohistochemical expression of various angiogenic factors in tissues from primary melanomas and metastases as well as their concentration in blood samples were examined. Strong expression of Heat Shock Protein 27 (HSP27) in metastases correlated significantly with complete or partial response to bevacizumab (p = 0.044). Furthermore, clinical benefit, i.e., complete or partial response or stable disease for at least 6 months, was more frequent in patients with strong expression of HSP27 in primary tumors (p = 0.046). Tissue expression of vascular endothelial growth factor (VEGF-A), its splicing variant VEGF165b or basic fibroblast growth factor (bFGF) did not correlate with response, and the concentration of HSP27, VEGF-A or bFGF measured in blood samples before treatment did not show predictive value. Further, microvessel density, proliferating microvessel density and presence of glomeruloid microvascular proliferations were assessed in sections of primary tumors and metastases. Microvessel density in primary melanomas was significantly higher in patients with clinical benefit than in non-responders (p = 0.042). In conclusion, our findings suggest that strong HSP27 expression in melanoma metastases predicts response to bevacizumab treatment.
2016-05-11T00:00:00ZInvestigation of predictive markers in patients with metastatic melanoma treated with bevacizumabhttp://hdl.handle.net/1956/15572
Investigation of predictive markers in patients with metastatic melanoma treated with bevacizumab
Schuster, Cornelia
Doctoral thesis
<p><strong>Background:</strong> The incidence of malignant melanoma is still rising among fair- skinned people worldwide, and it is among the three major cancer types in young adults in Norway. Progression free survival and overall survival have improved for metastatic melanoma, but there is still a need to improve treatment options. Only about 50% of the melanomas are BRAF mutated and not all patients are eligible to immunotherapy or respond to this kind of treatment. Therefore, further treatment options and validated predictive markers needs to be investigated.</p>
<p><strong>Purpose:</strong> This PhD project is based on a clinical Phase II trial that investigated efficacy and safety of bevacizumab monotherapy in patients with metastatic melanoma. Based on the encouraging results of a disease control rate of 31%, we wanted to investigate predictive markers in tissues and blood samples.</p>
<p><strong>Material and Methods:</strong> 35 patients with metastatic melanoma in progression were included in this clinical Phase II trial conducted at Haukeland University Hospital. Bevacizumab was given in a dosage of 10mg/kg every second week until disease progression or unacceptable toxicity. Blood pressure was monitored at every treatment cycle. The primary endpoint was objective response (OR) including patients with complete response (CR) or partial response (PR) according to RECIST guidelines as well as disease control (DC) including patients with stable disease (SD) for more than 6 months in addition. Tissues from primary tumors and metastases as well as blood samples were collected. BRAF and NRAS mutation status was assessed (Paper I).</p>
<p>In this work, we focused on investigations in serum and plasma samples taken before treatment with bevacizumab was started. We performed immunohistochemical staining of whole tissue sections from primary melanomas and metastases. Based on pre-specified hypotheses, we investigated the angiogenesis-related markers VEGF-A, its splicing variant VEGF-A165b, bFGF and HSP27 (Paper II). Microvessel density, the number of proliferating vessels and the presence of glomeruloid proliferations (GMPs) were also assessed in tissue samples. In addition, we analysed serum concentrations of VEGF-A, bFGF and HSP27 by ELISA (Paper II).</p>
<p>Furthermore, we investigated 60 angiogenesis-related proteins in serum samples by a multiplex array. Unsupervised hierarchical clustering as well as supervised analysis for particular proteins were performed. Candidate proteins that were associated with response to treatment were further validated by immunohistochemistry and ELISA (Paper III).</p>
<p><strong>Results:</strong> 6/35 patients had objective response (OR) to treatment with bevacizumab monotherapy and 5 more patients had stable disease, resulting in a disease control (DC) rate of 31%. Responses were observed independently of BRAF and NRAS mutation status. Development of early hypertension was associated with a better DC-rate and may serve as a clinical predictive marker (Paper I).</p>
<p>Strong expression of HSP27 in metastases was associated with objective response to bevacizumabmonotherapy. Strong expression of VEGF-A was associated with a higher number of proliferating vessels in primary melanomas and with a higher number of microvessels in metastases. However, microvessel density, the number of proliferating vessels or presence of GMPs in metastases were not associated with response to treatment. Serum concentration of VEGF-A, bFGF and HSP27 could not predict treatment response (Paper II).</p>
<p>Unsupervised hierarchical clustering of serum concentrations assessed by the multiplex array did not show any specific pattern. Proteins with a defined fold change difference between responders and non-responders were further investigated by specific analysis. Low serum concentration of Activin A as well as high serum concentrations of IL1b, uPAR and VEGF-A were associated with objective response to bevacizumab monotherapy. Single protein ELISA was performed for these candidate proteins but could not confirm the results from the multiplex array. However, strong expression by immunohistochemistry of Activin A, IL1b and uPAR in tumor cells from metastases was associated with objective response to bevacizumab monotherapy (Paper III).</p>
<p><strong>Conclusions:</strong> Treatment with bevacizumab monotherapy showed promising efficacy in patients with metastatic malignant melanoma in progression. Development of early hypertension may be a potential clinical predictor. We identified strong expression of HSP27, Activin A, IL1b and uPAR in metastases as possible predictive markers. Since our results are based on a single-arm trial with limited sample size, they have to be interpreted carefully. Validation in a larger randomized trial has to be performed.</p>
2016-11-22T00:00:00ZLaryngeal response patterns influence the efficacy of mechanical assisted cough in amyotrophic lateral sclerosishttp://hdl.handle.net/1956/15356
Laryngeal response patterns influence the efficacy of mechanical assisted cough in amyotrophic lateral sclerosis
Andersen, Tiina Maarit; Sandnes, Astrid; Brekka, Anne Kristine; Hilland, Magnus; Clemm, Hege; Fondenes, Ove; Tysnes, Ole Bjørn; Heimdal, John-Helge; Halvorsen, Thomas; Vollsæter, Maria; Røksund, Ola Drange
Journal article
<p>Background: Most patients with amyotrophic lateral sclerosis (ALS) are treated with mechanical insufflation&ndash;exsufflation (MI-E) in order to improve cough. This method often fails in ALS with bulbar involvement, allegedly due to upper-airway malfunction. We have studied this phenomenon in detail with laryngoscopy to unravel information that could lead to better treatment.</p>
<p>Methods: We conducted a cross-sectional study of 20 patients with ALS and 20 healthy age-matched and sex-matched volunteers. We used video-recorded flexible transnasal fibre-optic laryngoscopy during MI-E undertaken according to a standardised protocol, applying pressures of &plusmn;20 to &plusmn;50 cm H2O. Laryngeal movements were assessed from video files. ALS type and characteristics of upper and lower motor neuron symptoms were determined.</p>
<p>Results: At the supraglottic level, all patients with ALS and bulbar symptoms (n=14) adducted their laryngeal structures during insufflation. At the glottic level, initial abduction followed by subsequent adduction was observed in all patients with ALS during insufflation and exsufflation. Hypopharyngeal constriction during exsufflation was observed in all subjects, most prominently in patients with ALS and bulbar symptoms. Healthy subjects and patients with ALS and no bulbar symptoms (n=6) coordinated their cough well during MI-E.</p>
<p>Conclusions: Laryngoscopy during ongoing MI-E in patients with ALS and bulbar symptoms revealed laryngeal adduction especially during insufflation but also during exsufflation, thereby severely compromising the size of the laryngeal inlet in some patients. Individually customised settings can prevent this and thereby improve and extend the use of non-invasive MI-E.</p>
2016-01-01T00:00:00ZNanodiamond modified copolymer scaffolds affects tumour progression of early neoplastic oral keratinocyteshttp://hdl.handle.net/1956/15351
Nanodiamond modified copolymer scaffolds affects tumour progression of early neoplastic oral keratinocytes
Suliman, Salwa; Mustafa, Kamal Babikeir Eln; Krueger, Anke; Steinmüller-Nethl, Doris; Finne-Wistrand, Anna; Osdal, Tereza; Osman, Amani Hamza Ali; Sun, Yang; Parajuli, Himalaya; Waag, Thilo; Nickel, Joachim; Johannessen, Anne Christine; McCormack, Emmet; Costea, Daniela Elena
Journal article
This study aimed to evaluate the tumorigenic potential of functionalising poly(LLA-co-CL) scaffolds. The copolymer scaffolds were functionalised with nanodiamonds (nDP) or with nDP and physisorbed BMP-2 (nDP-PHY) to enhance osteoinductivity. Culturing early neoplastic dysplastic keratinocytes (DOKLuc) on nDP modified scaffolds reduced significantly their subsequent sphere formation ability and decreased significantly the cells' proliferation in the supra-basal layers of in vitro 3D oral neoplastic mucosa (3D-OT) when compared to DOKLuc previously cultured on nDP-PHY scaffolds. Using an in vivo non-invasive environmentally-induced oral carcinogenesis model, nDP scaffolds were observed to reduce bioluminescence intensity of tumours formed by DOKLuc + carcinoma associated fibroblasts (CAF). nDP modification was also found to promote differentiation of DOKLuc both in vitro in 3D-OT and in vivo in xenografts formed by DOKLuc alone. The nDP-PHY scaffold had the highest number of invasive tumours formed by DOKLuc + CAF outside the scaffold area compared to the nDP and control scaffolds. In conclusion, in vitro and in vivo results presented here demonstrate that nDP modified copolymer scaffolds are able to decrease the tumorigenic potential of DOKLuc, while confirming concerns for the therapeutic use of BMP-2 for reconstruction of bone defects in oral cancer patients due to its tumour promoting capabilities.
2016-07-01T00:00:00ZBiomarkers in breast cancer, with special focus on tumor cell proliferationhttp://hdl.handle.net/1956/15344
Biomarkers in breast cancer, with special focus on tumor cell proliferation
Knutsvik, Gøril
Doctoral thesis
<p>Background: Breast cancer is a heterogeneous disease encompassing distinct
subtypes that differ in incidence and prognosis. Better characterization of established
biomarkers and exploration of novel biomarkers and possible treatment targets are
important to improve prognostication and tailored therapy. A major challenge has
been to predict which patients who are likely to suffer from recurrence and thus may
benefit from adjuvant chemotherapy.</p>
<p>Objective: This study aimed to compare three proliferation markers across distinct
tissue categories, with association patterns and survival as end-points. Also, we aimed
to explore the protein expression and potential prognostic impact of the novel
proliferation-related biomarker QSOX1.</p>
<p>Materials and methods: The thesis is based on three papers where a prospective,
population-based series of breast cancer (n=534) was examined. In Paper I, the
proliferation marker Ki67 was assessed by immunohistochemistry across matched
samples of whole sections, WS (n=534), core needle biopsies, CNB (n=154) and
tissue microarrays, TMA (n=459). In Paper II, mitotic count (mitoses per mm2) was
assessed on H&E sections and PHH3 was examined by immunohistochemistry across
matched samples (WS, CNB, TMA), and compared with the Ki67 values. In Paper
III, QSOX1 expression was assessed by immunohistochemistry on TMA sections
(n=458).</p>
<p>Results: The proliferation markers (MC, Ki67, PHH3) showed significantly higher
counts when assessed on WS as compared to CNB and TMA (Paper I-II). Tumor
cell proliferation (MC, Ki67, PHH3) varied according to molecular subgroup with
highest proliferation in the triple negative subgroup and lowest proliferation in the
luminal category. In the luminal/HER2 negative subgroup, there were many
discordant cases and only fair agreement when assessing luminal A and B on WS as
compared to CNB and TMA (Paper I-II). Increased proliferation assessed by MC,
Ki67 and PHH3 across all three sample categories showed significant associations with high histologic grade and hormone receptor negativity (Paper I-II). In
univariate survival analysis, the prognostic impact of MC, Ki67 and PHH3 were
mostly retained across specimen categories. In multivariate Cox analysis, adjusting
for age, tumor size, histologic grade and nodal status, mitotic count and Ki67
maintained their independent associations with prognosis, whereas PHH3 did not
(Paper II). High expression of QSOX1 was associated with high histologic grade,
hormone receptor negativity, increased proliferation (MC, Ki67), and HER2
positivity (Paper III). High QSOX1 expression was more common among HER2+
and triple negative subgroups. In univariate survival analysis, cases with high
QSOX1 expression (SI=9) showed a 10 year survival probability of 67% compared to
89% for carcinomas with low QSOX1 levels (SI=0-6). QSOX1 expression showed
independent prognostic impact in multivariate Cox models adjusting for age,
histologic grade, tumor size and nodal status.</p>
<p>Conclusions: Assessment of proliferation markers on full sections, when available,
should be regarded as current best practice (Paper I-II). For assessment on core
needle biopsies, specimen specific thresholds should be considered. TMA is less
suited for assessment of proliferation in studies with potential clinical impact (Paper
I-II). Mitotic count might be used for sub-classification of the luminal group of breast
cancers (Paper II). High QSOX1 expression in tumor cells is a marker of more
aggressive breast cancer (Paper III).</p>
2016-10-31T00:00:00ZBlue-blocking glasses as additive treatment for mania: A randomized placebo-controlled trialhttp://hdl.handle.net/1956/15339
Blue-blocking glasses as additive treatment for mania: A randomized placebo-controlled trial
Henriksen, Tone Elise Gjøtterud; Skrede, Silje; Fasmer, Ole Bernt; Schøyen, Helle Kristine; Leskauskaite, Ieva; Bjørke-Bertheussen, Janette; Assmus, Jörg; Hamre, Børge; Grønli, Janne; Lund, Anders
Journal article
<p>Objectives: The discovery of the blue lightsensitive retinal photoreceptor responsible for signaling daytime to the brain suggested that light to the circadian system could be inhibited by using blue-blocking orange tinted glasses. Blue-blocking (BB) glasses are a potential treatment option for bipolar mania. We examined the effectiveness of BB glasses in hospitalized patients with bipolar disorder in a manic state.</p>
<p>Methods: In a single-blinded, randomized, placebo-controlled trial (RCT), eligible patients (with bipolar mania; age 18&ndash;70 years) were recruited from five clinics in Norway. Patients were assigned to BB glasses or placebo (clear glasses) from 6 p.m. to 8 a.m. for 7 days, in addition to treatment as usual. Symptoms were assessed daily by use of the Young Mania Rating Scale (YMRS). Motor activity was assessed by actigraphy, and compared to data from a healthy control group. Wearing glasses for one evening/night qualified for inclusion in the intention-to-treat analysis.</p>
<p>Results: From February 2012 to February 2015, 32 patients were enrolled. Eight patients dropped out and one was excluded, resulting in 12 patients in the BB group and 11 patients in the placebo group. The mean decline in YMRS score was 14.1 [95% confidence interval (CI): 9.7&ndash;18.5] in the BB group, and 1.7 (95% CI: &minus;4.0 to 7.4) in the placebo group, yielding an effect size of 1.86 (Cohen&#39;s d). In the BB group, one patient reported headache and two patients experienced easily reversible depressive symptoms.</p>
<p>Conclusions: This RCT shows that BB glasses are effective and feasible as add-on treatment for bipolar mania.</p>
2016-05-01T00:00:00ZNano-TiO2 penetration of oral mucosa: in vitro analysis using 3D organotypic human buccal mucosa modelshttp://hdl.handle.net/1956/15331
Nano-TiO2 penetration of oral mucosa: in vitro analysis using 3D organotypic human buccal mucosa models
Konstantinova, Victoria; Ibrahim, Mohamed; Lie, Stein Atle; Birkeland Salmorin, Eivind; Neppelberg, Evelyn; Marthinussen Cuida, Mihaela; Costea, Daniela Elena; Cimpan, Mihaela Roxana
Journal article
<p>BACKGROUND: Oral cavity is a doorway for a variety of products containing titanium dioxide (TiO2) nanoparticles (NPs) (nano-TiO2) such as food additives, oral healthcare products and dental materials. Their potential to penetrate and affect normal human oral mucosa is not yet determined.</p>
<p>OBJECTIVES: To evaluate the ability of nano-TiO2 to penetrate the in vitro reconstructed normal human buccal mucosa (RNHBM).</p>
<p>METHODS: RNHBM was generated from primary normal human oral keratinocytes and fibroblasts isolated from buccal oral mucosa of healthy patients (n = 6). The reconstructed tissues were exposed after 10 days to clinically relevant concentrations of spherical or spindle rutile nano-TiO2 in suspension for short (20 min) and longer time (24 h). Ultrahigh-resolution imaging (URI) microscopy (CytoVivaTM, Auburn, AL, USA) was used to assess the depth of penetration into reconstructed tissues.</p>
<p>RESULTS: Ultrahigh-resolution imaging microscopy demonstrated the presence of nano-TiO2 mostly in the epithelium of RNHBM at both 20 min and 24-h exposure, and this was shape and doze dependent at 24 h of exposure. The depth of penetration diminished in time at higher concentrations. The exposed epithelium showed increased desquamation but preserved thickness.</p>
<p>CONCLUSION: Nano-TiO2 is able to penetrate RNHBM and to activate its barrier function in a doze- and timedependent manner.</p>
2016-01-01T00:00:00ZEMG changes during continuous intraoperative neuromonitoring with sustained recurrent laryngeal nerve traction in a porcine modelhttp://hdl.handle.net/1956/15318
EMG changes during continuous intraoperative neuromonitoring with sustained recurrent laryngeal nerve traction in a porcine model
Brauckhoff, Katrin; Aas, Turid; Biermann, Martin; Husby, Paul
Journal article
<p>Purpose: Traction is the most common cause of injury to the recurrent laryngeal nerve (RLN) in endocrine neck surgery. The purpose of this study was to evaluate specific alterations to the electromyogram (EMG) and verify safe alarm limits in a porcine model of sustained traction of the RLN using continuous intraoperative neuromonitoring (C-IONM).</p>
<p>Methods: Sixteen Norwegian Landrace pigs were anesthetized and intubated with a tracheal tube with a stick-on laryngeal electrode. EMG was recorded at baseline (BL) and during sustained traction applied to each RLN until 70 % amplitude decrease from BL, and during 30-min recovery.</p>
<p>Results: In 29 nerves at risk (NAR), BL amplitude and latency values were 1098&thinsp;&plusmn;&thinsp;418 (586&ndash;2255) &mu;V (mean&thinsp;&plusmn;&thinsp;SD (range)) (right vagus) and 845&thinsp;&plusmn;&thinsp;289 (522&ndash;1634) &mu;V (left vagus), and 4.7&thinsp;&plusmn;&thinsp;0.5 (4.1&ndash;5.9) ms and 7.9&thinsp;&plusmn;&thinsp;0.8 (6.7&ndash;9.6) ms, respectively. At 50 % amplitude decrease, latency increased by 14.0&thinsp;&plusmn;&thinsp;5.7 % (right side) and 14.5&thinsp;&plusmn;&thinsp;9.1 % (left side) compared with BL. Corresponding values for 70 % amplitude depression were 17.9&thinsp;&plusmn;&thinsp;6.1 % and 17.3&thinsp;&plusmn;&thinsp;12.8 %. Traction time to 50 and 70 % amplitude decrease ranged from 3 to 133 min and 3.9&ndash;141 min, respectively. In 16 NAR (55 %), time from 50 to 70 % reduction in amplitude was &le;5 min, but in six NAR (21 %) &le;1 min. In only 11 (38 %) of 29 nerves, the amplitude recovered to more than 50 % of BL.</p>
<p>Conclusions: Latency increase may be the first warning of RLN stretch injury. Given the short interval between 50 and 70 % amplitude reduction of the EMG, amplitude reduction by 50 % can be taken as an appropriate alert limit.</p>
2016-01-01T00:00:00ZHelicopter-based emergency medical services for a sparsely populated region: A study of 42,500 dispatcheshttp://hdl.handle.net/1956/15316
Helicopter-based emergency medical services for a sparsely populated region: A study of 42,500 dispatches
Østerås, Øyvind; Brattebø, Guttorm; Heltne, Jon-Kenneth
Journal article
<p>Background: The Helicopter Emergency Medical Service (HEMS) in Norway is operated day and night, despite challenging geography and weather. In Western Norway, three ambulance helicopters, with a rapid response car as an alternative, cover close to 1 million inhabitants in an area of 45,000 km2. Our objective was to assess patterns of emergency medical problems and treatments in HEMS in a geographically large, but sparsely populated region.</p>
<p>Methods: Data from all HEMS dispatches during 2004&ndash;2013 were assessed retrospectively. Information was analyzed with respect to patient treatment and characteristics, in addition to variations in services use during the day, week, and seasons.</p>
<p>Results: A total of 42,456 dispatches were analyzed. One third of the patients encountered were severely ill or injured, and two thirds of these received advanced treatment. Median activation time and on-scene time in primary helicopter missions were 5 and 11 min, respectively. Most patients (95%) were reached within 45 min by helicopter or rapid response car. Patterns of use did not change. More than one third of all dispatches were declined or aborted, mostly due to no longer medical indication, bad weather conditions, or competing missions.</p>
<p>Conclusion: One third of the patients encountered were severely ill or injured, and more than two thirds of these received advanced treatment. HEMS use did not change over the 10-year period, however HEMS use peaked during daytime, weekends, and the summer. More than one third of all dispatches were declined or aborted.</p>
2016-05-01T00:00:00ZPatterns of motor activity in spontaneously hypertensive rats compared to Wistar Kyoto ratshttp://hdl.handle.net/1956/15301
Patterns of motor activity in spontaneously hypertensive rats compared to Wistar Kyoto rats
Fasmer, Ole Bernt; Johansen, Espen Borgå
Journal article
<p>Background: Increased motor activity is a defining characteristic of patients with ADHD, and spontaneously hypertensive rats have been suggested to be an animal model of this disorder. In the present study, we wanted to use linear and non-linear methods to explore differences in motor activity patterns in SHR/NCrl rats compared to Wistar Kyoto (WKY/NHsd) rats.</p>
<p>Methods: A total number of 42 rats (23 SHR/NCrl and 19 WKY/NHsd, male and female) were tested. At PND 51, the animals&rsquo; movements were video-recorded during an operant test procedure that lasted 90 min. Total activity level and velocity (mean and maximum), standard deviation (SD) and root mean square successive differences (RMSSD) were calculated. In addition, we used Fourier analysis, autocorrelations and two measures of complexity to characterize the time series; sample entropy and symbolic dynamics.</p>
<p>Results: The SHR/NCrl rats showed increased total activity levels in addition to increased mean and maximum velocity of movements. The variability measures, SD and RMSSD, were markedly lower in the SHR/NCrl compared to the WKY/NHsd rats. At the same time, the SHR/NCrl rats displayed a higher complexity of the time series, particularly with regard to the total activity level as evidenced by analyses of sample entropy and symbolic dynamics. Autocorrelation analyses also showed differences between the two strains. In the Fourier analysis, the SHR/NCrl rats had an increased variance in the high frequency part of the spectrum, corresponding to the time period of 9&ndash;17 s.</p>
<p>Conclusion: The findings show that in addition to increased total activity and velocity of movement, the organization of behavior is different in SHR/NCrl relative to WKY/NHsd controls. Compared to controls, behavioral variability is reduced in SHR/NCrl at an aggregate level, and, concomitantly, more complex and unpredictable from moment-tomoment. These finding emphasize the importance of the measures and methods used when characterizing behavioral variability. If valid for ADHD, the results indicate that decreased behavioral variability can co-exist with increased behavioral complexity, thus representing a challenge to current theories of variability in ADHD.</p>
2016-12-01T00:00:00ZImpact of EMG Changes in Continuous Vagal Nerve Monitoring in High-Risk Endocrine Neck Surgeryhttp://hdl.handle.net/1956/15275
Impact of EMG Changes in Continuous Vagal Nerve Monitoring in High-Risk Endocrine Neck Surgery
Brauckhoff, Katrin; Vik, Renate Kollevåg; Sandvik, Lorentz; Heimdal, John-Helge; Aas, Turid; Biermann, Martin; Brauckhoff, Michael
Journal article
<p>Background: Continuous vagal intraoperative neuromonitoring (CIONM) of the recurrent laryngeal nerve (RLN) may reduce the risk of RLN lesions during high-risk endocrine neck surgery such as operation for large goiter potentially requiring transsternal surgery, advanced thyroid cancer, and recurrence.</p>
<p>Methods: Fifty-five consecutive patients (41 female, median age 61 years, 87 nerves at risk) underwent high-risk endocrine neck surgery. CIONM was performed using the commercially available NIM-Response 3.0 nerve monitoring system with automatic periodic stimulation (APS) and matching endotracheal tube electrodes (Medtronic Inc.). All CIONM events (decreased amplitude/increased latency) were recorded.</p>
<p>Results: APS malfunction occurred on three sides (3 %). A total of 138 CIONM events were registered on 61 sides. Of 138, 47 (34 %) events were assessed as imminent (13 events) or potentially imminent (34 events) lesions, whereas 91 (66 %) were classified as artifacts. Loss of signal was observed in seven patients. Actions to restore the CIONM baseline were undertaken in 58/138 (42 %) events with a median 60 s required per action. Four RLN palsies (3 transient, 1 permanent) occurred: one in case of CIONM malfunction, two sudden without any significant previous CIONM event, and one without any CIONM event. The APS vagus electrode led to temporary damage to the vagus nerve in two patients.</p>
<p>Conclusions: CIONM may prevent RLN palsies by timely recognition of imminent nerve lesions. In high-risk endocrine neck surgery, CIONM may, however, be limited in its utility by system malfunction, direct harm to the vagus nerve, and particularly, inability to indicate RLN lesions ahead in time.</p>
2016-03-01T00:00:00ZHepatoid adenocarcinoma of the stomach - Proper identification and treatment remain a challengehttp://hdl.handle.net/1956/15245
Hepatoid adenocarcinoma of the stomach - Proper identification and treatment remain a challenge
Søreide, Jon Arne; Greve, Ole Jacob; Gudlaugsson, Einar; Størset, Svein
Journal article
<p>Objective: The term hepatoid adenocarcinoma (HAC) of the stomach was introduced three decades ago with the observation of high serum &alpha;-fetoprotein (AFP) levels in some gastric adenocarcinoma patients. This very rare gastric cancer patient subgroup is likely frequently misdiagnosed.</p>
<p>Material: Two patients who were recently diagnosed with HAC of the stomach at our institution are presented. We also performed a structured literature search and reviewed pertinent articles to provide knowledge to improve the proper identification, diagnosis and management of patients with gastric HAC.</p>
<p>Results: HAC is a rare subgroup of gastric carcinoma with poor prognosis. Clinical management of this population may be challenging. The scientific literature is largely based on very small patient series or case reports, and the evidence for proper decision making and management is considered weak.</p>
<p>Conclusion: All physicians involved in the diagnosis and treatment of patients with gastric cancer should pay attention to this rare subgroup to improve identification.</p>
2016-01-01T00:00:00ZEnd Stage Renal Disease Predicts Increased Risk of Death in First Degree Relatives in the Norwegian Populationhttp://hdl.handle.net/1956/15233
End Stage Renal Disease Predicts Increased Risk of Death in First Degree Relatives in the Norwegian Population
Skrunes, Rannveig; Svarstad, Einar; Reisæter, Anna Varberg; Marti, Hans-Petter; Vikse, Bjørn Egil
Journal article
<p>Background: Increased risk of end stage renal disease (ESRD) and death in Norwegian living kidney donors has been reported, most of the donors were related to the recipient. The present study investigates risk of death in first degree relatives of ESRD patients.</p>
<p>Methods: The Norwegian Population Registry, The Norwegian Cause of Death Registry and the Norwegian Renal Registry were linked. All citizens born in Norway, alive in 1960 and with at least one registered first degree relative were included; individuals who died during the first year of life were excluded. A cohort-design was used, ESRD in a first degree relative was the main exposure variable and death and causes of death were the main outcome variables. Cox regression statistics were used to investigate mortality risks.</p>
<p>Results: 5 130 600 individuals were included, 27 508 had at least one first degree relative with ESRD. 828 022 died during follow-up, of whom 4105 had a first degree relative with ESRD. Adjusted hazard ratio (aHR) for death was 1.13 (1.09&ndash;1.16) in individuals with a relative with ESRD compared to those without a relative with ESRD. Excluding known hereditary renal disease, aHR decreased to 1.12 (1.09&ndash;1.15). Cardiovascular death aHR was 1.15 (1.10&ndash;1.21), of which cerebrovascular death 1.34 (1.22&ndash;1.50). aHR for death due to non-hereditary renal/ureteric disease was 2.29 (1.81&ndash;2.91) with renal failure 1.80 (1.26&ndash;2.56) and glomerular disease 5.69 (3.88&ndash;8.34) as main contributors. Diabetes mellitus death aHR was 1.68 (1.35&ndash;2.10). Absolute mortality risks increased most for the oldest cohorts with excess mortality of 148 per 100.000 person years for the cohort born 1920&ndash;39 and 218 for the cohort born 1900&ndash;1919.</p>
<p>Conclusions: ESRD in first degree relatives was associated with increased hazard ratio for death. Death due to cardiovascular disease, renal disease and diabetes mellitus increased the most.</p>
2016-11-09T00:00:00ZVascularization and Host Response in Bone Tissue Engineeringhttp://hdl.handle.net/1956/15230
Vascularization and Host Response in Bone Tissue Engineering
Bartaula-Brevik, Sushma
Doctoral thesis
<p>The major hurdle in the survival of a tissue-engineered construct after implantation is
vascularization. Pre-vascularization is one of the proposed methods to achieve
vascularization in tissue-engineered constructs. This thesis is centered on prevascularization
of the tissue-engineered construct and local host response upon
implantation in vivo.</p>
<p>In Study I, mesenchymal stem cells (MSC) with and without endothelial cells (EC)
were cultured in normoxic and hypoxic conditions in vitro. The conditioned medium
from each group were evaluated with functional assays. The secretomes from hypoxic
mono- and co-culture groups demonstrated increased wound healing and tube
formation in vitro when compared with their normoxic counter-parts.</p>
<p>In Study II, pre-vascularized constructs were generated by co-culturing MSC and EC
in three dimensional copolymer poly (LLA-co-DXO) scaffolds. After in vivo
implantation, local tissue response was evaluated with gene and protein analysis. The
constructs with both MSC and EC were associated with decreased pro-inflammatory
cytokines compared with those having MSC alone.</p>
<p>In Study III, three-dimensional constructs with either MSC or EC alone were
implanted and their angiogenic and immunogenic property were evaluated. The
expressions of anti-inflammatory and vasculogenic cytokines were higher in the
constructs with EC than in the constructs with MSC. Furthermore, down-regulation
of pro-inflammatory cytokines was observed.</p>
<p>In conclusion, MSC in combination with EC developed microvessels-like structures
before implantation in vivo. Hypoxia, a common consequence after implantation of
constructs, accelerated wound healing and tube formation via paracrine effect of
MSC. Combining these two effects might lead to inosculation and survival of a graft.
Addition of EC improved the immunomodulatory property of MSC.</p>
2016-12-07T00:00:00ZCircadian rest-activity rhythms during benzodiazepine tapering covered by melatonin versus placebo add-on: data derived from a randomized clinical trialhttp://hdl.handle.net/1956/13161
Circadian rest-activity rhythms during benzodiazepine tapering covered by melatonin versus placebo add-on: data derived from a randomized clinical trial
Baandrup, Lone; Fasmer, Ole Bernt; Glenthøj, Birte Yding; Jennum, Poul Jørgen
Journal article
<p>Background: Patients with severe mental illness often suffer from disruptions in circadian rest-activity cycles, which might partly be attributed to ongoing psychopharmacological medication. Benzodiazepines are frequently prescribed for prolonged periods despite recommendations of only short-term usage. Melatonin, a naturally occurring nocturnal hormone, has the potential to stabilize disrupted circadian rhythmicity. Our aim was to investigate how prolonged-release melatonin affects rest-activity patterns in medicated patients with severe mental illness and if benzodiazepine dose reduction is associated with changes in circadian rhythm parameters.</p>
<p>Method: Data were derived from a randomized, double-blinded clinical trial with 24 weeks follow-up. Participants were randomized to add-on treatment with prolonged-release melatonin (2 mg) or matching placebo, and usual benzodiazepine dosage was gradually tapered. Here we report the results of 72 h of actigraphic assessment of activity-rest cycles performed pre and post tapering. Changes in rest-activity rhythm parameters between the melatonin and placebo group were analyzed using the univariate general linear model. Change in activity counts per 6 h, from baseline to follow-up, in the whole sample was analyzed using paired samples t-test.</p>
<p>Results: A subsample of 48 patients participated in the actigraphic assessment: 20 in the melatonin group and 28 in the placebo group. Rest-activity cycles varied from regular to highly disrupted. Melatonin significantly increased the interdaily stability and at a trend level decreased the intradaily variability compared with placebo. Benzodiazepine dose reduction was not associated with these circadian rhythm parameters. Activity counts were generally higher after benzodiazepine dose reduction compared with pre tapering, but differences did not reach statistical significance.</p>
<p>Conclusion: Our data suggest melatonin as an aid during benzodiazepine withdrawal for patients distressed by disrupted circadian rest-activity cycles. Benzodiazepine tapering might result in diminished sedentary behavior but further research is needed.</p>
2016-10-13T00:00:00ZKartlegging av jernstatus og betydningen av kosthold og sosioøkonomisk status hos 14-15 -åringer i Bergen Kommunehttp://hdl.handle.net/1956/13028
Kartlegging av jernstatus og betydningen av kosthold og sosioøkonomisk status hos 14-15 -åringer i Bergen Kommune
Lode, Miriam
Master thesis
Iron deficiency is one of the most prominent nutritional deficiencies worldwide. Despite several attempts to reduce both iron deficiency and anemia, it has become a persistent problem, also in the industrialized parts of the world. Adolescents are one of the groups who are at risk, mainly due to increased demands by growth. In particular, girls at this age are highly disposed because of a greater loss of iron through menstruation. Few studies have examined iron status of Norwegian adolescents from the last decades and this thesis will provide an updated survey by one of the largest sample investigated in Norway so far. Objective. This thesis is a part of an intervention study in which 785 students from secondary schools in Bergen municipality aged 14-15 years were invited, whereas 481 students agreed to join. We have collected venous samples of serum ferritin from 464 students. In addition we examined the importance of diet using a semi-quantitative food frequency questionnaire answered by 470 students and a second questionnaire was sent to the parents to obtain information about their socioeconomic status, whereas 374 answered. Results. Iron deficiency, defined as serum ferritin levels below 15 µg/L occurred in 9.1% of the participants. When we excluded participants who took iron supplement, the prevalence increased to 9.9%. Logistic regression analysis showed that the girls had a higher odds of developing iron deficiency compared with the boys (Odds Ratio [OR]=2.82, 95% Confidence Interval [CI]=1.38 to 5.75, P=0.004), whereas 12.8% of the girls and only 5% of the boys had concentrations of serum ferritin below 15 µg/L. There were few significant associations between the participants` diet and serum ferritin. Intake of red meat showed a weak positive correlation with serum ferritin, but only among girls (Spearman`s correlation coefficient [Rho]=0.152, P=0.018). A negative correlation between serum ferritin and consumption of dairy products was found in boys (Rho=-0.212, P=0.002). Socioeconomic status was not seen to have any decisive impact on the participants´ serum ferritin or food intake in this study population. Conclusions. This thesis suggest that iron deficiency is a declining problem among Norwegian adolescents compared with previous surveys. With every tenth middle school student suffering from iron deficiency in an affluent country like Norway, this is still not desirable. The differences in genders may suggest that a greater focus towards girls should be given in this age group. By conducting routine surveys one might be able to prevent or early detect iron deficiency and iron deficiency anemia.
2016-05-15T00:00:00ZIodine status in Norwegian preschool children and significance of dietary sources of iodine and parental socio-economic factors - A cross-sectional studyhttp://hdl.handle.net/1956/13027
Iodine status in Norwegian preschool children and significance of dietary sources of iodine and parental socio-economic factors - A cross-sectional study
Odland, Mathilde
Master thesis
Iodine is an essential trace element with important physiological effects in the human body. Iodine is necessary for thyroid hormone synthesis. The hormones are needed for tissue development in the central nervous system, growth and brain development in children, and regulation of basal metabolic rate and macronutrient metabolism. Iodine deficiency is still a global threat despite international efforts to eliminate the condition. In recent years, major progress have been made towards elimination of iodine deficiency due to introduction of universal salt iodization programs. However, iodine deficiency is still the number one cause of preventable mental retardation in children. In Norway, goiter prevalence was high prior to introduction of fortification of cow fodder in 1950. Since then, iodine status of the Norwegian population have gradually improved. However, several studies have suggested that subgroups of the Norwegian population may be susceptible to iodine deficiency due to low intake of iodine-rich food sources including seafood and dairy products. Studies on iodine status in Norwegian preschool children (aged 4-6 years) are old and lacking. Study aims: Main aim of the present thesis was to determine and evaluate the iodine status of preschool children living in Bergen. Specific aims included investigations of possible associations between urinary iodine concentration and iodine-rich food sources and parental socio-economic factors. Associations between parental socio-economic factors and the children's intake of iodine-containing foods were also examined. Methods and materials: The present thesis is part of a larger intervention study. Habitual dietary intake was assessed by a semi-quantitative food frequency questionnaire. Iodine concentration was determined by inductively coupled plasma-mass spectrometry in non-fasting, spot urine samples. Results: Approximately 50% of the children consumed fish and other seafood less frequently than current Norwegian recommendations of two to three servings per week. Nearly all children consumed dairy products daily. The iodine status of the preschool children was adequate (133 µg/L). Intake of fatty fish (OR = 1.95, 95% CI = 1.01-3.77, p = 0.048) and sweet milk (OR = 2.17, 95% CI = 1.07-4.38, p = 0.031) were associated with sufficient iodine status. Weak correlations were observed between iodine status and intake of iodine-rich food sources and between iodine status and parental socio-economic factors. In addition, unadjusted logistic regression models found higher socio-economic status to be associated with increased likelihood of a higher intake of seafood for dinner and dairy products among the children. Conclusions: The preschool children in this study had adequate iodine status, and intake of sweet milk and fatty fish were significant predictors of sufficient iodine status. Parental socio-economic status seemed to be associated with the children's intake of seafood and dairy products.
2016-05-15T00:00:00ZThe effect of a low FODMAP diet in addition to a gluten free diet on symptoms and quality of life in patients with coeliac disease and IBS-like symptoms: A randomized, controlled clinical studyhttp://hdl.handle.net/1956/13025
The effect of a low FODMAP diet in addition to a gluten free diet on symptoms and quality of life in patients with coeliac disease and IBS-like symptoms: A randomized, controlled clinical study
Nuland, Kamilla
Master thesis
Around 20-30% of coeliac disease patients have IBS-like symptoms. The low FODMAP diet (low in fermentable oligo-, di-, monosaccharides and polyols) is used as treatment for irritable bowel syndrome (IBS) to reduce gastrointestinal symptoms. As far as we know, there are no published papers on low FODMAP diet to patients with coeliac disease. Purpose: We wanted to investigate whether patients with coeliac disease and IBS-like symptoms could have a benefit from using this diet in addition to their gluten free diet, especially regarding abdominal symptoms and quality of life. Traditionally, these have been given advice to further eliminate traces of gluten in their diet. We compared this strategy to a reduction in FODMAPs as instructed by a clinical dietitian. We also wanted to investigate whether a low FODMAP diet would have any effect on the gut microbiota and the degree of fermentation by gut bacteria, measured with breath tests and stool samples (another Master's Thesis). The objective was to investigate whether this is a treatment which can be recommended for coeliac patients with IBS-like symptoms or not. Method: Forty patients with coeliac disease-, and IBS-like symptoms confirmed by the Rome III criteria and score 75 or more on IBS-SSS (Symptom Severity Scale) were included in the study. They were randomized into two groups. Group A followed a more strict gluten free diet for six weeks and were supposed to exclude all wheat starch and food labelled traces of gluten" from their diet. Patients in group B continued to follow a traditional gluten free diet in addition to following a low FODMAP diet for six weeks. Symptoms (Irritable bowel syndrome- Symptom Severity Scale) were recorded at baseline, three and six weeks. Quality of life (SF-36), 4 days prospective dietary intake records, blood tests, breath tests and stool samples were carried out at baseline and after six weeks on their diets. Compliance and satisfaction with the two diets were evaluated by VAS-scales after 6 weeks, and 1 month after the intervention ended in group B. All the patients were given dietary counselling by master students in clinical nutrition. Dietist Net Free was used to calculate the amount of FODMAPs in the diets at baseline and at six weeks. Statistics: T-tests, non-parametric tests, categorical tests, ANOVA, Friedman and correlation tests. Results: Twenty patients were included in each group; group A (18F/2M, age 39±15) and group B (15F/5M, age 43±12). At baseline, 42.5% had constipation problems (IBS-C), 27.5% diarrhoea problems (IBS-D) and 30% both (IBS-M). At baseline, 20% in group A vs. 10% in group B had mild IBS, 45% vs. 65% moderate and 35% vs. 25% severe IBS symptoms. After six weeks there were statistically significant differences between the groups (p=0.0425); 10% vs. 25% were in remission, 15% vs. 45% had mild IBS, 65% vs. 25% moderate and 10% vs. 5% severe. There were 5 patients in group A and 1 in group B that had raised anti-transglutaminase 2 IgA- levels, vs. 2 and 3 with raised anti-deamidated gliadin IgG-levels. The FODMAP intake decreased statistically significant from 7.7 (2.7-19.2) g/day at baseline to 1.3 (0.9-2.1) g/day at six weeks in group B (p=0.0001), vs. a non- significant decrease from 14.5 (10.9-21.6) to12.1...
2016-05-17T00:00:00ZPrevalence of dysbiosis and microbiotic effect of the low FODMAP diet in coeliac disease patients with IBS-like symptomshttp://hdl.handle.net/1956/13024
Prevalence of dysbiosis and microbiotic effect of the low FODMAP diet in coeliac disease patients with IBS-like symptoms
Strindmo, Ida Serine Melhus
Master thesis
A subgroup of coeliac disease patients have IBS (irritable bowel syndrome)-like symptoms despite following a gluten free diet (GFD). We wanted to compare the microbiota in these patients with an IBS and a healthy population, and look at changes during a low FODMAP (fermentable oligo-, di-, monosaccharides and polyols) diet versus a stricter GFD. We also wanted to look at the effect of diet on symptom relief in these patients. Methods: 40 celiac disease patients with IBS-like symptoms confirmed by the Rome III-criteria and IBS-SSS (symptom severity scale)=75 were compared to Norwegian IBS and healthy cohorts, and randomized into two groups. Group A followed a stricter GFD, whilst patients in group B reduced FODMAPs in their GFD. Both groups followed their diet for six weeks. Faecal samples were collected at baseline and 6 weeks and IBS-SSS at baseline, 3 and 6 weeks. Hydrogen breath test was performed at baseline and after six weeks. The faecal samples were analysed by Genetic Analysis for bacteria and Dysbiosis Index (DI) 1-5, where DI>2 is considered clinically relevant. Statistics: T-test, Mann-Whitney U, RM one way ANOVA, Fisher's linear discriminant analysis. Results: FODMAPs were reduced from 11.5 to 1.6g/day (p=0.0001) in group B, and IBS-SSS score improved in both group A (p=0.0022) and group B (p=0.0001). 45% of the patients had dysbiosis at baseline, compared to 73% in IBS (p=0.0091) and 16% in healthy controls (p=0.0007), with a mean score of 2.5±1.1 versus 3.0±1.0 and 1.7±0.7, respectively. Several bacterial genera were significantly altered at baseline compared to healthy controls, including Bacillus and Prevotella. In group A (18F/2M, age 39±15), dysbiosis stayed constant on diet, but more patients had severe dysbiosis (DI>3), 15% vs. 25% (p=0.85). In group B (15F/5M, age 44±12), fewer patients had dysbiosis after diet, 60% vs. 50% (p=0.79). There was a statistically significant reduction in the genus Bacteroides after the LFD compared to the stricter GFD (p=0.024). Responders to low FODMAP diet (IBS-SSS score reduction >100) had a distinctive microbiota pattern with less Lactobacilli and Firmicutes (Clostridia), and more Atopobium at baseline. There were no reduction in the AUC for hydrogen after six weeks on a low FODMAP diet (p=0.926). Conclusion: Celiac disease patients with IBS- like symptoms had less severe dysbiosis than an IBS-population, but more than healthy controls. This study give evidence for the effect of the low FODMAP diet for symptom relief in these patients. We found that the level of Lactobacilli, Firmicutes (Clostridia) and Atopobium predicted response to the low FODMAP diet.
2016-05-17T00:00:00ZNutritional Screening and Treatment of Malnutrition at a Haematological Ward - An economical perspectivehttp://hdl.handle.net/1956/13022
Nutritional Screening and Treatment of Malnutrition at a Haematological Ward - An economical perspective
Trollebø, Marte Almenning
Master thesis
When a patient is admitted to the hospital he or she should be screened for malnutrition within the first 24 hours. If the patient is identified as being at risk, appropriate treatment should be given, and then the patient receives the appropriate ICD-10 code for malnutrition at discharge. This tells us that malnutrition has been treated, and should ensure that the ward receives reimbursement for the treatment given. The Norwegian health authorities gave the recommendations for prevention and treatment of hospital malnutrition in 2009, but are these guidelines being followed in clinical practice? Malnutrition is present in 19% - 60% of hospitalized patients, depending on the population under study and the screening tools used. Malnutrition is known to increase morbidity and length of stay (LOS), and therefore result in increased health care and hospital costs. It is estimated that it is possible to save an annual amount of 800 million Norwegian kroner, by identifying and treating malnutrition in Norwegian hospitals. Aims: The aim of this study was to evaluate the screening routines and nutritional treatment given at a haematology ward in a Norwegian university hospital, to evaluate if better routines can have an economic impact based on identification and coding for malnutrition, length of stay, and nutritional treatment. Methods: The thesis had a retrospective part where the above mentioned outcomes were studied, and a prospective part to evaluate the impacts of an intervention consisting of an instructive course. The routines for nutritional screening and treatment were evaluated by collecting data from the electronic medical record. The intervention was aimed towards the nurses. They received guidance and lectures on screening and nutritional treatment. Results: Medical records of 302 patients were retrospectively evaluated during two periods. 137 patients in the first period, and 165 patients in the second. In the first period no patients were screened for malnutrition, while 15 (9%) were screened in the second period (p under 0.001). There was not a significant difference in routines for coding malnutrition (8 in the first, 12 in second. P-value = 0, 651), and hence no difference in potential reimbursement. A significant decrease in LOS was observed, from a median of 5 to 4 days (p = 0,015), which was estimated to give a potential reduction of costs equivalent to NOK 7 289 350.00 annually. There was no significant difference in patients receiving nutritional treatment, individual nutritional plan or referral to clinical dietician. At the same time there was no significant difference in the kind of nutritional treatment given (parenteral nutrition, enteral nutrition, and oral nutritional supplements). Conclusions: An intervention consisting of an instructive course, with relevant lectures and training nurses in screening, resulted in a significant increase of screened patients. The intervention had no impact on routines for the coding of malnutrition, and the diagnosis related group (DRG) reimbursement for malnutrition. LOS was reduced, and this could potentially result in reduced costs. Our study indicates that the routines for nutritional screening are deficient, and that there is still room for improvement of nutritional routines at the haematology ward.
2016-05-18T00:00:00ZThe obesogenic potential of high fat/high protein diets is determined by both amino acid- and fatty acid composition of the protein source usedhttp://hdl.handle.net/1956/13021
The obesogenic potential of high fat/high protein diets is determined by both amino acid- and fatty acid composition of the protein source used
Korsmo, Karianne
Master thesis
Studies in rodents have found that high protein diets differ in obesogenic potential depending on the protein source used. Varied changes in morphology of brown adipose tissue, an important metabolic organ in mice and rats, have also been observed. Whether diversity in obesogenic potential of different protein sources is caused by amino acid composition, fatty acid composition or a combination of both is unknown. Further, little is known about causes and consequences of changes in brown adipose tissue morphology. Methods: Male C57BL/6J BomTac mice were fed different high-fat/high-protein diets. Casein, cod, pangasius and chicken was used as protein sources, but they also provided different amounts and types of fat to the diet. Pangasius, high in omega-6 fatty acids and with similar amino acid composition as cod, was used to distinguish between the effect of amino acid- and fatty acid composition. Four groups were fed ad libitum, and one group was fed restricted amounts of the chicken-based diet in order to evaluate the impact of weight gain on brown adipose tissue activity and morphology. We studied the effect of different protein sources on body weight development, energy intake, body composition, glucose homeostasis and gene expression in interscapular brown adipose tissue. Body composition was determined by MRI-scan and histology was carried out to examine changes in adipose tissue morphology. Insulin tolerance test and oral glucose tolerance test were performed to assess insulin sensitivity and glucose tolerance. Uncoupling protein-1 (UCP1) expression in brown adipose tissue (BAT) was analyzed by real time-qPCR and immunohistochemistry. Results: A high-fat/high-protein diet based on chicken was obesogenic relative to the one based on cod, whereas the pangasius-based diet had an intermediate effect. Calorie restriction attenuated changes in BAT morphology caused by the chicken-based diet. Similar classic BAT morphology as the one observed in lean chicken- fed mice was also observed in mice fed casein and pangasius. Little differences was observed in gene expression, but immunohistochemistry revealed higher expression of UCP1 in mice fed casein, pangasius and chicken in restricted amounts. Conclusion: Both amino acid- and fatty acid composition determines the obesogenic potential of different protein sources in high-fat/high- protein diets. Changes in BAT morphology and activity are partially decided by body weight, but pangasius as protein- and fat source attenuates this effect. Mice fed casein remains lean with a classic BAT morphology.
2016-05-12T00:00:00ZLow birth weight and risk of progressive kidney disease. Epidemiological and morphological studieshttp://hdl.handle.net/1956/12996
Low birth weight and risk of progressive kidney disease. Epidemiological and morphological studies
Ruggajo, Paschal Joseph
Doctoral thesis
<p>Background: Low Birth Weight (LBW) and Small for Gestation Age (SGA) are surrogate markers for fetal
undernutrition and are associated with impaired nephron development in utero as suggested by the Brenner`s
hypothesis. We investigated whether familial factors explain the association between LBW and ESRD,
whether LBW and/or SGA predict progression to ESRD in IgAN patients and whether LBW and/or SGA is
associated with altered glomerular size or density in young IgAN patients with preserved renal function.
Methods: We linked medical birth data from the Medical Birth Registry of Norway (MBR), sibling data
from the Norwegian Population Registry, ESRD data from the Norwegian Renal Registry (NRR) and kidney
biopsy data from the Norwegian Kidney Biopsy Registry (NKBR). For Paper I and II, data were analysed in
a retrospective cohort study design. Exposure variables for Paper I were LBW/ SGA in the participant
and/or LBW/SGA in at least 1 sibling. For Paper II, exposure variables were LBW/ SGA among a cohort of
IgAN patients. Outcome variable for Paper I and II was development of ESRD and data were analysed with
cox regression statistics. For paper III we selected IgAN patients and control patients registered in the
NKBR who had registered birth weight in the MBR and preserved renal function (i.e e GFR≥60 ml/min/1.73m2) at time of diagnosis. Differences in glomerular density and volume were investigated
between subjects with or without LBW/SGA as well as between IgAN patients and controls.</p>
<p>Results: In Paper I, we found that of 1,852,080 included individuals, 527 developed ESRD. Compared with
individuals without LBW and with no siblings with LBW, individuals without LBW but with a sibling with
LBW had an hazard ratio (HR) for ESRD of 1.20 (95% CI, 0.91-1.59), individuals with LBW but no
siblings with LBW had an HR of 1.59 (95% CI, 1.18 - 2.14), and individuals with LBW and a sibling with
LBW had an HR of 1.78 (95% CI, 1.26-2.53). Similar results were observed for individuals who were SGA.
In Paper II we found that as compared to patients without LBW, patients with LBW had an increased risk of
progression to ESRD with an HR of 2.0 (1.1-3.7) for the total cohort, 2.2 (1.1-4.4) for male and 1.3 (0.30-
5.8) for female). Similar results were observed for SGA but further analyses suggested that subjects with
both LBW and SGA had the highest risk. In paper III we found that compared to IgAN patients without LBW or SGA, IgAN patients with LBW and/or SGA had larger glomerular area (16235±3744 vs 14036±3502 μm3, p-value 0.04), significant in males but not females.</p>
<p>Conclusion; Having been born LBW and/or SGA was associated with higher risk for all-cause ESRD
independent of other familial factors shared among siblings. Further, LBW and/or SGA was associated with
increased risk for progression to ESRD among young male IgAN patients and were also associated with
larger glomeruli (a marker of congenital nephron deficit). Taken together, our results support the Brenner
hypothesis.</p>
2016-10-19T00:00:00ZLow birth weight and risk of progression to end stage renal disease in IgA nephropathy - A retrospective registry-based cohort studyhttp://hdl.handle.net/1956/12993
Low birth weight and risk of progression to end stage renal disease in IgA nephropathy - A retrospective registry-based cohort study
Ruggajo, Paschal Joseph; Svarstad, Einar; Leh, Sabine Maria; Marti, Hans-Peter; Reisæter, Anna Varberg; Vikse, Bjørn Egil
Journal article
<p>Background:
Low Birth Weight (LBW) is a surrogate for fetal undernutrition and is associated with impaired nephron development in utero. In this study, we investigate whether having been born LBW and/or small for gestational age (SGA) predict progression to ESRD in IgA nephropathy (IgAN) patients.</p>
<p>Study Design:
Retrospective registry-based cohort study.</p>
<p>Settings & Participants:
The Medical Birth Registry has recorded all births since 1967 and the Norwegian Renal Registry has recorded all patients with ESRD since 1980. Based on data from the Norwegian Kidney Biopsy Registry we included all patients diagnosed with IgAN in Norway from 1988–2013. These registries were linked and we analysed risk of progression to ESRD associated with LBW (defined as birth weight less than the 10th percentile) and/or SGA (defined as birth weight less than the 10th percentile for gestational week) by Cox regression statistics.</p>
<p>Results:
We included 471 patients, of whom 74 developed ESRD. As compared to patients without LBW, patients with LBW had a hazard ratio (HR) of 2.0 (95% confidence interval 1.1–3.7) for the total cohort, 2.2 (1.1–4.4) for males and 1.3 (0.30–5.8) for females. Corresponding HRs for SGA were 2.2 (1.1–4.2), 2.7 (1.4–5.5) and 0.8 (0.10–5.9). Further analyses showed that as compared to patients with neither LBW nor SGA, patients with either SGA or LBW did not have significantly increased risks (HRs of 1.3–1.4) but patients who were both LBW and SGA had an increased risk (HR 3.2 (1.5–6.8).</p>
<p>Limitation:
Mean duration of follow-up only 10 years and maximum age only 46 years.</p>
<p>Conclusion:
Among IgAN patients, LBW and/or SGA was associated with increased risk for progression to ESRD, the association was stronger in males.</p>
2016-04-19T00:00:00ZInfluence of hospital procedure volume on the risk of revision in knee arthroplasty surgeryhttp://hdl.handle.net/1956/12968
Influence of hospital procedure volume on the risk of revision in knee arthroplasty surgery
Badawy, Mona
Doctoral thesis
<p>The knee is a complex joint consisting of three anatomically and kinematically
different compartments; the medial, the lateral and the patellofemoral compartment.
When developing painful and disabling osteoarthritis (OA), there are different
treatment options. Conservative treatment consisting of pain medication, injection
therapy, physiotherapy and exercises can delay or prevent surgical treatment in many
patients. However, many OA patients will need knee replacement surgery if all other
fails. Most of these patients need a total knee arthroplasty (TKA), but in many cases
with isolated unicondylar OA, unicompartmental knee replacement (UKA) is
sufficient.</p>
<p>Knee replacement surgery is rapidly increasing in Norway and worldwide. Both total
knee and unicompartmental knee arthroplasty surgery are technically difficult
procedures with multiple possible pitfalls perioperatively. The procedures require
thorough knowledge of the bony and soft tissue anatomy and kinematics, as well as
proper surgical technique and experience with the implants and concomitant
instruments.</p>
<p>The purpose of Paper I was to investigate whether there was a correlation between
annual hospital procedure volume and the risk of revision in total knee arthroplasty
using data from the Norwegian Arthroplasty Register. We found a significantly
higher revision risk following total knee arthroplasty in low-volume hospitals in
comparison to high-volume hospitals.</p>
<p>In Paper II we compared high and low-volume hospitals regarding risk of revision in
patients operated with the Oxford III UKA based on data from the NAR. We also
investigated possible variations in the reasons for revision. Our interpretation was that higher hospital volumes were beneficial for improved survival of the Oxford III
implant.</p>
<p>Paper III was an expansion and further development of Paper II, investigating the
effect of hospital procedure caseload on the risk of revision upon the usage of Oxford
III UKA in the four Nordic countries using data from the Nordic Arthroplasty
Register Association database. In this study we used a combination of three different
methods of calculating annual hospital procedure volume. Lower volume hospitals
had inferior results in all 3 methods of analysis as well as in the combined model with
a 3-year moving average estimate.</p>
<p>In conclusion, to optimize knee arthroplasty results and to avoid high rates of
revision, acceptable procedure volumes should be achieved. TKA patients operated in
hospitals performing more than 100 cases per year had a lower risk of revision. UKA
patients operated in hospitals performing &gt;40 cases per year had the lowest risk of
revision in the NAR, whereas UKA patients in the NARA had a higher risk of
revision if operated in hospitals performing less than 25 per year.</p>
Figures no. 1, 3, 8, 12 and 13 are removed from the version available in BORA
due to copyright issues.
2016-10-07T00:00:00ZInfluence of Hospital Volume on Revision Rate After Total Knee Arthroplasty with Cementhttp://hdl.handle.net/1956/12961
Influence of Hospital Volume on Revision Rate After Total Knee Arthroplasty with Cement
Badawy, Mona; Espehaug, Birgitte; Indrekvam, Kari; Engesæter, Lars B.; Havelin, Leif Ivar; Furnes, Ove
Journal article
<p>Background: The number of total knee replacements has substantially increased worldwide over the past ten years.
Several studies have indicated a correlation between high hospital procedure volume and decreased morbidity and
mortality following total knee arthroplasty. The purpose of the present study was to evaluate whether there is a correlation
between procedure volume and the risk of revision following total knee arthroplasty with use of hospital volume data from
the Norwegian Arthroplasty Register.</p>
<p>Methods: Thirty-seven thousand, three hundred and eighty-one total knee arthroplasties that were reported to the
Norwegian Arthroplasty Register from 1994 to 2010 were used to examine the annual procedure volume per hospital.
Hospital volume was divided into five categories according to the number of procedures performed annually: one to twentyfour
(low volume), twenty-five to forty-nine (medium volume), fifty to ninety-nine (medium volume), 100 to 149 (high
volume), and ‡150 (high volume). Cox regression (adjusted for age, sex, and diagnosis) was used to estimate the proportion
of procedures without revision and the risk ratio (RR) of revision. Analyses were also performed for two commonly used
prosthesis brands combined.</p>
<p>Results: The rate of prosthetic survival at ten years was 92.5% (95% confidence interval, 91.5 to 93.4) for hospitals with
an annual volume of one to twenty-four procedures and 95.5% (95% confidence interval, 94.1 to 97.0) for hospitals with an
annual volume of ‡150 procedures. We found a significantly lower risk of revision for hospitals with an annual volume of
100 to 149 procedures (relative risk = 0.73 [95% confidence interval, 0.56 to 0.96], p = 0.03) and ‡150 procedures
(relative risk = 0.73 [95% confidence interval, 0.54 to 1.00], p = 0.05) compared with hospitals with an annual volume of
one to twenty-four procedures. Similar results were found when we analyzed two commonly used prosthesis brands.</p>
<p>Conclusions: In the present study, there was a significantly higher rate of revision knee arthroplasties at low-volume
hospitals as compared with high-volume hospitals.</p>
2013-01-01T00:00:00ZExcellent response of intramedullary Erdheim-Chester disease to vemurafenib: a case reporthttp://hdl.handle.net/1956/12922
Excellent response of intramedullary Erdheim-Chester disease to vemurafenib: a case report
Tzoulis, Charalampos; Schwarzlmüller, Thomas; Søfteland, Eirik; Neckelmann, Gesche; Biermann, Martin; Haroche, Julien; Straume, Oddbjørn; Gjerde, Ivar Otto; Vintermyr, Olav Karsten
Journal article
<p><strong>Background:</strong> Erdheim-Chester disease is a rare histiocytosis characterized by multi-systemic organ involvement. Immune-modulating agents such as interferon-alpha have limited success and the disorder is progressive and causes high morbidity and mortality. Treatment with the BRAF-inhibitor vemurafenib has recently produced substantial improvement in three patients with Erdheim-Chester disease expressing the p. V600E BRAF mutation. The disorder commonly affects the central nervous system and it is not yet known whether vemurafenib can reverse intra-axial infiltration and the resulting neurological impairment.</p> <p><strong>Case presentation:</strong> In this work, we report for the first time an excellent clinical response to vemurafenib in a Norwegian patient with debilitating progressive spastic paraparesis due to intra-axial infiltration of the thoracic spinal cord. The patient had been unresponsive to interferon-alpha. Low dose vemurafenib (720 mg daily) for a period of three months resulted in significant tumor shrinkage by >60% and regression of contrast enhancement and fluorodeoxyglucose uptake on positron-emission tomography. The patient’s spastic paraparesis and gait function improved dramatically. She currently walks unaided and reports a substantially improved quality of life.</p> <p><strong>Conclusion:</strong> Our findings show that vemurafenib therapy, even at low doses, can be effective for the treatment of intra-axial central nervous system involvement in BRAF-positive Erdheim-Chester disease.</p>
2015-04-30T00:00:00ZWhy do some countries approve a cancer drug and others don’t?http://hdl.handle.net/1956/12913
Why do some countries approve a cancer drug and others don’t?
Pujolras, Laia Maynou; Cairns, John Alexander
Journal article
The term drug reimbursement describes the policy system that determines whether or not a drug is entitled to reimbursement within the healthcare system. Countries make different decisions regarding which cancer treatments to routinely provide. As a result, depending on the cancer drug-indication and the country assessing it, the decision can be Favourable, Favourable with restrictions or Non-Favourable. The main objective of this paper is to describe the differences in drug reimbursement decisions on cancer drugs across 10 European countries. This aim is achieved through testing a number of hypotheses that can explain the differences in these specific reimbursement decisions. First of all, we collect data on cancer drug decisions for 10 European countries, from 2002 to 2014. Secondly, the hypotheses are tested on this database. The results show that Social Health Insurance systems tend to take more Favourable decisions than the tax-based systems, that cost-effective drug-indications have a higher probability of reimbursement and that other countries are more likely to make a Favourable decision if NICE also make it. Moreover, our findings also corroborate that an economic evaluation requirement reduces the number of Favourable decisions, and that, during the global financial crisis, the number of Favourable decisions has been reduced, compared to Non-Favourable and restricted. To sum up, characteristics of the drug reimbursement system, drug particularities and the socioeconomic situation are the main factors determining the differences across countries.
2015-06-01T00:00:00ZNo increase in response rate by adding a web response option to a postal population survey: A randomized trialhttp://hdl.handle.net/1956/12910
No increase in response rate by adding a web response option to a postal population survey: A randomized trial
Brøgger, Jan; Nystad, Wenche; Cappelen, Inger; Bakke, Per
Journal article
<p><strong>Background:</strong> There is substantial interest in use of the Internet for surveys, but there have been few health-oriented, large, randomized trials of general population surveys on the Internet. It is unclear whether providing the option to respond via Internet increases the response rate, and to what degree the results will differ.</p>
<p><strong>Objective:</strong> The aim of the study was to evaluate changes in response rate and outcomes in a postal respiratory health survey by adding an optional Web response alternative.<p>
<p><strong>Methods:</strong> This was a randomized trial of a random sample of 4213 permanent residents of Norway, aged 20-40 years. Participants were randomized into a traditional survey arm, where they were asked to return the survey by mail, and an arm where they were also offered the option to respond via a Web form.</p>
<p><strong>Results:</strong> A total of 1928/4213 subjects responded, a response rate of 45.8% across both arms. The total response rate was 44.8% (944/2105) in the postal plus optional Internet response arm and 46.7% (984/2108) in the usual postal survey arm, with no statistically significant difference between the randomized groups (P = .24). In the optional Internet arm, 8.3% (175/2105) of the sample responded using the Internet and 36.5% (769/2105) responded by post. Thus, Internet response was chosen by 18.5% (175/944) of those who replied in the optional Internet arm. In the multivariate analysis, Internet response was associated with being male, frequency and type of Internet access (home users more likely to respond by Internet than work users), and smoking habit, with current smokers being more likely to be Internet responders. 57% preferred postal response (1102/1928), 38% preferred Internet response (733/1928), and 3% preferred telephone interview (54/1928), with no difference between randomization arms (P = .56). But among those who indicated that they preferred the Internet response and who were randomized to the optional Internet arm, only 47% actually chose the Internet response. Asthma prevalence was higher among participants choosing the Internet response mode (16.7% vs 12.4%).</p>
<p><strong>Conclusions:</strong> We failed to increase survey response rates by adding an optional Internet response. Asthma diagnosis was higher in the Internet response group, suggesting nonresponse bias. Method comparison studies should be carried out before Internet studies are accepted in new populations or new subject matters.</p>
2007-12-31T00:00:00ZRefeeding syndrome in patients with Anorexia Nervosa. Procedures to detect and treat patients at risk of refeeding syndrome in regional departments of eating disorders in Norway and nutrient contents of the basic reference menu at Regional Department of Eating Disorders (RASP)http://hdl.handle.net/1956/12907
Refeeding syndrome in patients with Anorexia Nervosa. Procedures to detect and treat patients at risk of refeeding syndrome in regional departments of eating disorders in Norway and nutrient contents of the basic reference menu at Regional Department of Eating Disorders (RASP)
Hjellen, Margrete
Master thesis
Background Anorexia nervosa (AN) is a disorder recognized by underweight and psychiatric symptoms, and some patients are at risk of developing refeeding syndrome (RFS). AN patients may experience metabolic disturbances and severe symptoms during refeeding, and international guidelines in how to refeed AN patients at risk of RFS varies. The regional departments of eating disorders (EDs) in Norway treat about 100-200 patients every year with AN, and a survey investigating procedures have not been performed before. Aim This master thesis has investigated how physicians and registered dietitians (RDs) in the departments of EDs in Norway consider RFS, and how they refeed and monitor patients with AN. Due to the complications and problems that may occur during refeeding in high-risk groups like AN, it was of interest to investigate if procedures, knowledge and awareness varied between the ED units and if the basic reference menu at RASP contain the energy and micronutrients that is recommended for AN patients during refeeding. Method Procedures, questionnaires and analysis of the basic reference menu at RASP have been collected and analyzed. The procedures were collected by contacting the head physicians at the different regional departments of EDs by mail. The master student designed the questionnaire, with assistance from the RDs and supervisor at RASP. The four-week rollover dinner menu at RASP was weighed, photographed and nutritional content calculated. The average nutrient content of the dinners was analyzed together with the other meals (breakfast, lunch, and evening meal) in the basic menu/ and half of the basic menu to evaluate the yield of important nutrients trough one day. Results Three out of six regional departments of EDs have a procedure to identify and/or treat patients at risk of RFS. Initial refeeding range of energy in the procedures varied between 10-30 kcal/kg/body weight, or half dietary lists (1000-1500 kcal). RFS is a rare syndrome in the ED III units. Only one clinician at one of the ED units had ever seen a patient with full-blown RFS. The basic reference menu at RASP covers the recommendations of most nutrients. Half basic reference menu contains more energy than most international guidelines recommended for patients at risk of RFS. The energy contents in dinner portions in the basic reference menu contain an average of about 480kcal. Conclusion The procedures of RFS vary between the regional departments of EDs in Norway. A closer collaboration between the units may be favorable, and all units ought to have procedures to identify and treat patients at risk of RFS. The knowledge and awareness of RFS among physicians and RDs working at an ED unit in Norway are good. However, the questionnaire detected that there are some uncertainties both among the physicians and RDs about the definition of RFS. The energy prescribed in Halv grunnmeny" is higher than most of the international guidelines for initial refeeding of patients at risk of RFS. The basic reference menu makes an important frame for and is a good guidance for the milieu therapists that serve the patients during the nutritional rehabilitation at RASP. Supplementation of omega 3, vitamin D and iron should be assessed.
2016-05-23T00:00:00ZPrealbumin as a nutritional marker in normal and hyperemesis pregnancies - a case-control studyhttp://hdl.handle.net/1956/12884
Prealbumin as a nutritional marker in normal and hyperemesis pregnancies - a case-control study
Zybkina, Olga
Master thesis
Objective: Hyperemesis gravidarum (HG) affects 1% of pregnancies and is potentially harmful for mother and foetus. Prealbumin is a marker of nutritional status. We wanted to investigate whether prealbumin level was associated with severity and nutritional risks of NVP (nausea and vomiting in pregnancy). Methods: A case-control study including 92 hospitalized patients with hyperemesis gravidarum and 32 healthy controls. Serum Prealbumin was correlated to clinical and biochemical nutritional parameters, including 24h recall food-diary. Results: HG patients had longer gestational length than controls (median 8.6 versus 7.0 weeks, p<0.001). Otherwise, the groups were similar regarding pre-pregnant BMI, parity, proportion of earlier pregnancies complicated with HG in and weight at inclusion. The prealbumin levels were significant lower in HG versus controls: median 0.19 g/L versus 0.23 g/L (95% CI 0.18-0.20 and 0.19-0.25 , p<0.001). Compared to the control group HG patients had significantly lower 24h energy intake (median 653 kcal versus 1790, p<0.001), larger weight-change at inclusion (median –3 kg versus +1 kg, p<0.001), higher percentage of ketonuria +3 (69% versus 3% p<0.001) and higher PUQE-score (Pregnancy Unique Quantification of Emesis and nausea) median 13, 95% CI 13-14 versus 6, 95% CI 5-8). Prealbumin level , 24 h caloric and protein intake significantly decreased while weight-loss and ketonuria increased across severity of NVP as classified by the three tiered PUQE-score <6, 7-12 and 13-15 (all p ≤ 0.004). Prealbumin level was significantly correlated to 24 h protein intake, Pearson Correlation =0.401 (p= 0.001, two-tailed). Conclusion: Prealbumin-measuring validates patients with severe NVP/HG as being at high nutritional risk.; Bakgrunn: Uttalt svangerskapskvalme, Hyperemesis gravidarum (HG), er en tilstand som rammer ca. 1% av alle gravide. Ubehandlet kan tilstanden føre til alvorlige væske-/elektrolyttforstyrrelser og underernæring hos kvinnen. Det kan bli farlig både for mor og barn. Prealbumin brukes som markør på underernæring. Vi ønsket å vurdere om prealbumin nivå hos gravide samsvarer med alvorlighetsgrad og ernæringsmessige risiko ved svangerskapskvalme. Metode: En case-kontroll studie blant 92 innlagte pasienter med hyperemesis gravidarum og 32 friske kontroller. Serum prealbumin ble korrelert til kliniske og biokjemiske ernærings parametre, inkludert 24-timers matinntak. Resultater: HG pasienter hadde lengre svangerskapslengde enn kontrollene (median 8,6 versus 7,0 uker, p <0,001). Ellers var gruppene like angående pre-gravid BMI, paritet, andel med HG i tidligere svangerskap og vekt ved inklusjon. Prealbumin nivåene var signifikant lavere i HG versus kontroller: median 0,19 g/L sammenlignet med 0,23 g/L (95% CI 0,18-0,20 og 0,19-0,25 , p<0.001). Sammenlignet med kontrollgruppen hadde HG pasienter signifikant lavere 24-timers energiinntak (median 653 kcal versus 1790, p <0,001), større vekt-endring ved inklusjon (median -3 kg versus +1 kg, p <0,001) høyere prosentandel av ketonuri + 3 (69% versus 3% p <0,001) og høyere SUKK-skår (SvangerskapsUtløst Kvalme Kvantifisering ) median 13, 9 5% CI 13-14 versus 6, 95% CI 5-8). Prealbumin nivå, 24-timers kalori- og proteininntak sank betydelig mens vekttap og ketonuri økte med økende alvorlighetsgrad av svangerskapsutløst kvalme klassifisert som tre kategorier SUKK-skår: <6, 7-12 og 13-15 (alle p ≤0.004). Prealbumin nivået var signifikant korrelert til 24-timer protein inntak, Pearson korrelasjon = 0,401 (p = 0,001, to-sidig). Konklusjon: prealbumin-måling validerer at pasienter med alvorlig svangerskapsutløst kvalme/hyperemesis gravidarum utsatt for høy ernæringsmessig risiko.
2016-05-18T00:00:00ZImproving pancreas surgery over time: Performance factors related to transition of care and patient volumehttp://hdl.handle.net/1956/12876
Improving pancreas surgery over time: Performance factors related to transition of care and patient volume
Søreide, Jon Arne; Sandvik, Oddvar Mathias; Søreide, Kjetil
Journal article
<p><strong>Background:</strong> Pancreas surgery has evolved with better diagnostic imaging, changing indications, and improved patient selection. Outside high-volume tertiary centers, the documented effect of evolution in care and volumes are limited. Thus, we aimed to review indications and outcomes in pancreas surgery during the transition from community-based hospital to a university hospital. </p>
<p><strong>Methods:</strong> All pancreatic surgeries performed between 1986 and 2012 within a well-defined Norwegian population were identified from the hospital's database. Indications and postoperative outcomes, including mortality, were investigated.</p>
<p><strong>Results:</strong> Of the 219 included patients (54% males; median age, 64 years), 150 (69%) underwent pancreatoduodenectomy; 55 (25%), distal resection; and 5 (2%), enucleation. The annual number of operations increased during the study period (from &lt;10/yr to &gt;20/yr). Most patients (169; 77%) underwent surgery for suspected malignancy. The 30-day mortality decreased significantly over time among patients treated for pancreatic cancer (from 16.1% to 3.5%; p = 0.012). Over time, significant reductions in median hospitalization time (19 versus 12 days; p &lt; 0.001), re-operation rate (37.1% versus 8.4%; p &lt; 0.001), and median ICU stay (3 versus 0 days; p &lt; 0.001) were observed.</p>
<p><strong>Conclusion:</strong> The transition to university hospital and increase in volume has led to significant improvements in several performance metrics and reduced postoperative mortality. We believe improved perioperative management and focused, multidisciplinary care-bundles to be of importance.</p>
2016-06-29T00:00:00ZOn the diagnosis of early stage Prostate Cancer with an emphasis on Prostate Cancer Gene 3 (PCA3) and Real-Time Elastography (RTE)http://hdl.handle.net/1956/12840
On the diagnosis of early stage Prostate Cancer with an emphasis on Prostate Cancer Gene 3 (PCA3) and Real-Time Elastography (RTE)
Nygård, Yngve
Doctoral thesis
<p>Aims: To investigate real-time elastography (RTE} and prostate cancer gene 3 (PCA3} to see if these emerging markers/methods could contribute to a faster and more precise diagnosis and also to investigate the possibility of a better selection of patients in need of prostate biopsies.</p>
<p>Material and methods: Paper I: 40 consecutive patients planned for radical prostatectomy (RP} was investigated with RTE and PCA3 prior of RP. The results were compared to the whole-mount section pathology of the RP specimen. Paper II-IV: 127 consecutive patients planned for initial prostate biopsies were included. They were first examined with DRE for determination of clinical stage and for the prostatic massage needed before PCA3 analysis. Then they were examined with RTE and RTE targeted biopsies were obtained from hard lesions. Then a transrectal ultrasound guided systematic 10-core biopsy was performed in all patients.</p>
<p>Results: Paper I: Using PCA3 score with cut off of 35, 26 patients had a positive PCA3 test and 11 patients had a false negative test. The largest tumour with correct location was found in 73% and at least one tumour was found in 89%. Only one patient had both a negative RTE and PCA3 score leading to a total detection rate of 97%. Paper II: 64 patients were diagnosed with PC in the initial biopsy setting. The RTE targeted biopsies had a higher frequency of positive cores and also a trend towards a higher fraction of PC in the targeted biopsy cores than in the cores from the systematic biopsies (42% vs. 33%}. RTE was found to be an independent marker for the detection of high-risk PC. Per region of interest (ROI) a negative predictive value (NPV) of 97% was found for high grade PC with Gleason grade 4+3, score 7 and higher. Paper III: The systematic initial biopsies were used for the analyses. PC was diagnosed in 59 patients. PCA3 was tested for the cut-off values 21 and 35. The sensitivity/specificity was 71%/ 72% using 35 as cut-off and 81%/55% using 21 as cut-off respectively. Hansen&#39;s nomogram was valid for our cohort. PCA3 contributed significantly to the performance of the nomogram, a threshold value of 20 as biopsy decision seems to be safe. Paper IV: This paper also includes a follow-up period with a mean observation time of 46.7 (range 41- 55) months. Included are the results from the initial biopsies and also the results of eventual repeat biopsies. If both RTE and PCA3 are negative there is a low probability of detecting aggressive PC. The combined use of RTE and PCA3 lead to a NPV of 90% for the group of intermediate- and high-risk PC together, for the high-risk group NPV was 100%.</p>
<p>Conclusions: RTE has the ability of detecting PC and can be used for detection and also for targeted biopsies. PCA3 can be used in an initial biopsy setting and it contributes significantly to the area under the curve when applied to a nomogram. The combined use of PCA3 and RTE is better than the methods used alone.</p>
2016-09-23T00:00:00ZVitamin D status and cardiovascular disease. Observational studies in patients who underwent coronary angiographyhttp://hdl.handle.net/1956/12732
Vitamin D status and cardiovascular disease. Observational studies in patients who underwent coronary angiography
Degerud, Eirik Magnus Meek
Doctoral thesis
<p>Background: Vitamin D is required to maintain a healthy cardiovascular system, but
it is unknown whether variation in vitamin D status in the general population is
physiologically relevant to development of cardiovascular diseases (CVDs).</p>
<p>Aim: To study vitamin D status and investigate the associations of vitamin D status
with atherosclerosis progression, all-cause and CVD mortality.</p>
<p>Methods: Observational data from patients in Western-Norway with suspected
coronary artery disease were used (n=4116). Vitamin D status was assessed by the
measurement of plasma 25-hydroxyvitamin D (25OHD) concentrations,
atherosclerosis progression by repeat coronary angiography and survival data
obtained from national registries.</p>
<p>Results: Mean 25OHD most strongly associated with seasonality, adiposity and cod
liver oil consumption. Seasonal variation in 25OHD differed by age. During winter
and summer ~50% and ~80% of the participants were vitamin D sufficient,
respectively. When modelling baseline values, cosinor models most accurately
predicted follow-up values for patients with repeated measurements of 25OHD.
Baseline concentrations of 25OHD were not associated with atherosclerosis
progression after ~1 year of follow-up, but were inversely associated with a higher
risk of all-cause and cardiovascular mortality after ~12 years of follow-up. Despite a
linear tendency, non-linearity was observed in the relationship with all-cause
mortality, with higher risk among individuals with 25OHD concentrations below 42.5
nmol/l and above 100 nmol/l in comparison to those between 42.5 – 100 nmol/l.</p>
<p>Conclusions: Seasonal variation has a strong influence on vitamin D status and
researchers should consider cosinor models when adjusting for seasonality. A high
frequency of insufficiency during winter indicates inadequate dietary intakes despite
a high frequency of cod liver oil use in this population. Vitamin D status was
inversely associated with a higher risk of all-cause and CVD mortality, but not associated with subclinical progression of atherosclerosis. The relationship with allcause
mortality was J-shaped, with increased risk also among a smaller segment of
participants with high 25OHD concentrations.</p>
2016-01-19T00:00:00ZCosinor modelling of seasonal variation in 25-hydroxyvitamin D concentrations in cardiovascular patients in Norwayhttp://hdl.handle.net/1956/12717
Cosinor modelling of seasonal variation in 25-hydroxyvitamin D concentrations in cardiovascular patients in Norway
Degerud, Eirik Magnus Meek; Hoff, Rune; Nygård, Ottar; Strand, Elin; Nilsen, Dennis W. T.; Nordrehaug, Jan Erik; Midttun, Øivind; Ueland, Per Magne; De Vogel, Stefan; Dierkes, Jutta
Journal article
<p>Background/Objectives:
Seasonal variation may reduce the validity of 25-hydroxyvitamin D (25OHD) as a biomarker of vitamin D status. Here we aimed to identify potential determinants of seasonal variation in 25OHD concentrations and to evaluate cosinor modelling as a method to adjust single 25OHD measurements for seasonal variation.</p>
<p>Subjects/Methods:
In Caucasian cardiovascular patients (1999–2004), we measured 25OHD by liquid chromatography tandem mass spectrometry in 4116 baseline and 528 follow-up samples. To baseline values, we fitted a cosinor model for monthly concentrations of 25OHD. Using the model, we estimated each patient’s adjusted annual 25OHD value. Further, we studied how covariates affected the annual mean 25OHD concentration and seasonal variation of the study cohort. To evaluate the model, we predicted follow-up measurements with and without covariates and compared accuracy with carrying forward baseline values and linear regression adjusting for season, common approaches in research and clinical practice, respectively.</p>
<p>Results:
The annual mean (59.6 nmol/l) was associated with participants’ age, gender, smoking status, body mass, physical activity level, diabetes diagnosis, vitamin D supplement use and study site (adjusted models, P&lt;0.05). Seasonal 25OHD variation was 15.8 nmol/l, and older age (&gt;62 years) was associated with less variation (adjusted model, P=0.025). Prediction of follow-up measurements was more accurate with the cosinor model compared with the other approaches (P&lt;0.05). Adding covariates to cosinor models did not improve prediction (P&gt;0.05).</p>
<p>Conclusions:
We find cosinor models suitable and flexible for analysing and adjusting for seasonal variation in 25OHD concentrations, which is influenced by age.</p>
2016-01-01T00:00:00ZEarly neurological worsening in acute ischaemic stroke patientshttp://hdl.handle.net/1956/12694
Early neurological worsening in acute ischaemic stroke patients
Nacu, Aliona; Bringeland, Gerd Haga; Khanevski, Andrej; Thomassen, Lars; Waje-Andreassen, Ulrike; Næss, Halvor
Journal article
<p>Objectives:
Neurological worsening in acute ischaemic stroke patients is common with significant morbidity and mortality.</p>
<p>Aims:
To determine the factors associated with early neurological worsening within the first 9 h after onset of acute ischaemic stroke.</p>
<p>Materials & methods:
The National Institute of Health Stroke Scale (NIHSS) was used to assess stroke severity. Early neurological worsening was defined as NIHSS score increase ≥4 NIHSS points within 9 h of symptom onset compared to NIHSS score within 3 h of symptom onset. Patients with early neurological worsening were compared to patients with unchanged or improved NIHSS scores.</p>
<p>Results:
Of the 2484 patients admitted with ischaemic stroke, 552 patients had NIHSS score within 3 h of symptom onset, and 44 (8.0%) experienced early neurological worsening. The median NIHSS on admission was 8.4 in both groups. Early neurological worsening was associated with low body temperature on admission (P = 0.01), proximal compared to distal MCA occlusion (P = 0.007) and with ipsilateral internal carotid artery stenosis &gt;50% or occlusion (P = 0.04). Early neurological worsening was associated with higher NIHSS day 7 (P &lt; 0.001) and higher mortality within 7 days of stroke onset (P = 0.005).</p>
<p>Conclusions:
Early neurological worsening has serious consequences for the short-term outcome for patients with acute ischaemic stroke and is associated with low body temperature on admission, and with extracranially and intracranially large-vessel stenosis or occlusion.</p>
2016-01-01T00:00:00ZAge dependency of ischaemic stroke subtypes and vascular risk factors in western Norway: The Bergen Norwegian Stroke Cooperation Studyhttp://hdl.handle.net/1956/12693
Age dependency of ischaemic stroke subtypes and vascular risk factors in western Norway: The Bergen Norwegian Stroke Cooperation Study
Nacu, Aliona; Fromm, Annette; Sand, Kristin Modalsli; Waje-Andreassen, Ulrike; Thomassen, Lars; Næss, Halvor
Journal article
<p>Objectives:
Age dependency of acute ischaemic stroke aetiology and vascular risk factors have not been adequately evaluated in stroke patients in Norway. Aims of this study were to evaluate how stroke subtypes and vascular risk factors vary with age in a western Norway stroke population.</p>
<p>Materials and methods:
Patients aged 15–100 years consecutively admitted to our neurovascular centre with acute ischaemic stroke between 2006 and 2012 were included. The study population was categorized as young (15–49 years), middle-aged (50–74 years) or elderly (≥75 years). Stroke aetiology was defined by TOAST criteria. Risk factors and history of cardiovascular disease were recorded.</p>
<p>Results:
In total, 2484 patients with acute cerebral infarction were included: 1418 were males (57.3%). Mean age was 70.8 years (SD ± 14.9), 228 patients were young, 1126 middle-aged, and 1130 were elderly. The proportion of large-artery atherosclerosis and of small-vessel occlusion was highest among middle-aged patients. The proportion of cardioembolism was high at all ages, especially among the elderly. The proportion of stroke of other determined cause was highest among young patients. Some risk factors (diabetes mellitus, active smoking, angina pectoris, prior stroke and peripheral artery disease) decreased among the elderly. The proportions of several potential causes increased with age.</p>
<p>Conclusion:
The proportion of stroke subtypes and vascular risk factors are age dependent. Age 50–74 years constitutes the period in life where cardiovascular risk factors become manifest and stroke subtypes change.</p>
2016-03-01T00:00:00ZPredictive factors for time to recurrence, treatment and post-recurrence survival in patients with initially resected colorectal liver metastaseshttp://hdl.handle.net/1956/12607
Predictive factors for time to recurrence, treatment and post-recurrence survival in patients with initially resected colorectal liver metastases
Angelsen, Jon-Helge; Viste, Asgaut; Løes, Inger Marie; Eide, Geir Egil; Hoem, Dag; Sorbye, Halfdan; Horn, Arild
Journal article
<p>Background:
Despite progress in resection for colorectal liver metastases (CLM), the majority of patients experience recurrence. We aimed to evaluate factors influencing time to recurrence (TTR), treatment and post-recurrence survival (PRS) related to site of recurrence.</p>
<p>Methods:
This is a retrospective population-based cohort study (1998–2012) of consecutive patients without extrahepatic disease treated with resection for CLM in a referral centre.</p>
<p>Results:
A total of 311 patients underwent resection for CLM. After a median follow-up of 4.2 years (range 1.2–15.2), 209 (67.4 %) patients developed recurrence, hepatic 90, extrahepatic 59 and both 60. Median TTR was 14.0 months, and 5-year recurrence-free status was 25.7 %. Five- and 10-year overall survival (OS) was 38.8 and 22.0 %, respectively. Median OS was 45 months. A multivariate analysis displayed synchronous disease (hazard ratio (HR) 1.50), American Society of Anaesthesiologists (ASA) score (HR 1.40), increasing number (HR 1.24) and size of metastases (HR 1.08) to shorten TTR (all p &lt; 0.05). Perioperative chemotherapy (n = 59) increased overall TTR (HR 0.63) and overall survival (OS; HR 0.55). Hepatic TTR was correlated to synchronous disease (HR 2.07), number of lesions (HR 1.20), R1 resection (HR 2.00) and ASA score (HR 1.69), whereas extrahepatic TTR was correlated to N stage of the primary (HR 1.79), number (HR 1.27) and size of metastases (HR 1.16). Single-site recurrence was most common (135 of 209, 64.5 %), while 58 patients had double- and 16 triple-site relapses. Median PRS was 24.3 months. There was a difference in median PRS (months) according to site of relapse: liver 30.5, lung 32.3, abdominal 22.0, liver and lung 14.3, others 14.8 (p = 0.002). Repeated liver resections were performed in n = 57 patients resulting in 40.6 months median OS and 36.8 % 5-year OS.</p>
<p>Conclusions:
An adverse overall TTR was correlated to number and size of metastases, ASA score and synchronous disease. Perioperative chemotherapy increased TTR and OS after surgery for CLM. Patients with solitary post-resection relapse in the liver or lungs had the potential for longevity due to multimodal treatment.</p>
2015-12-03T00:00:00ZAdult pancreatic hemangioma in pregnancy – concerns and considerations of a rare casehttp://hdl.handle.net/1956/12568
Adult pancreatic hemangioma in pregnancy – concerns and considerations of a rare case
Søreide, Jon Arne; Greve, Ole Jakob; Gudlaugsson, Einar
Journal article
<p>Background:
Pancreatic tumors in pregnancy are rare but clinically challenging. Careful diagnostic workup, including appropriate imaging examinations, should be performed to evaluate surgery indications and timing . In the present case a diagnosis of an adult pancreatic hemangioma was made. We were not able to identify a similar case in the very sparse literature on this rare disease.</p>
<p>Case presentation:
A 30-year-old woman at 12 weeks of gestation was diagnosed with a large pancreatic tumor having a cystic pattern based on imaging. Although the preoperative diagnosis was uncertain, patient preference and clinical symptoms and signs suggested surgery. Open distal pancreatic resection including splenectomy was performed, and complete resection of the large cystic tumor was successfully achieved, with no postoperative complications. Although a solid pseudopapillary epithelial neoplasm (SPEN) was suspected, specimen morphology, including immunohistochemistry, supported the diagnosis of an adult benign pancreatic hemangioma.</p>
<p>Conclusion:
Although mucinous cystic neoplasm (MCN) and adenocarcinoma are the most common pancreatic tumors during pregnancy, various other malignant and benign lesions can be encountered. This report adds to the very small number of pancreatic hemangiomas reported in the literature and involves the first patient diagnosed with this rare condition during pregnancy. Careful clinical considerations regarding diagnostic workup and treatments are required to ensure that mother and child receive the best possible care.</p>
2015-10-30T00:00:00ZLinear and non-linear analyses of Conner’s Continuous Performance Test-II discriminate adult patients with attention deficit hyperactivity disorder from patients with mood and anxiety disordershttp://hdl.handle.net/1956/12555
Linear and non-linear analyses of Conner’s Continuous Performance Test-II discriminate adult patients with attention deficit hyperactivity disorder from patients with mood and anxiety disorders
Fasmer, Ole Bernt; Mjeldheim, Kristin; Førland, Wenche; Hansen, Anita Lill; Syrstad, Vigdis Elin Giæver; Ødegaard, Ketil Joachim; Berle, Jan Øystein
Journal article
<p>Background:
Attention Deficit Hyperactivity Disorder (ADHD) is a heterogeneous disorder. Therefore it is important to look for factors that can contribute to better diagnosis and classification of these patients. The aims of the study were to characterize adult psychiatric out-patients with a mixture of mood, anxiety and attentional problems using an objective neuropsychological test of attention combined with an assessment of mood instability.</p>
<p>Method:
Newly referred patients (n = 99; aged 18–65 years) requiring diagnostic evaluation of ADHD, mood or anxiety disorders were recruited, and were given a comprehensive diagnostic evaluation including the self-report form of the cyclothymic temperament scale and Conner’s Continuous Performance Test II (CPT-II). In addition to the traditional measures from this test we have extracted raw data and analysed time series using linear and non-linear mathematical methods.</p>
<p>Results:
Fifty patients fulfilled criteria for ADHD, while 49 did not, and were given other psychiatric diagnoses (clinical controls). When compared to the clinical controls the ADHD patients had more omission and commission errors, and higher reaction time variability. Analyses of response times showed higher values for skewness in the ADHD patients, and lower values for sample entropy and symbolic dynamics. Among the ADHD patients 59 % fulfilled criteria for a cyclothymic temperament, and this group had higher reaction time variability and lower scores on complexity than the group without this temperament.</p>
<p>Conclusion:
The CPT-II is a useful instrument in the assessment of ADHD in adult patients. Additional information from this test was obtained by analyzing response times using linear and non-linear methods, and this showed that ADHD patients with a cyclothymic temperament were different from those without this temperament.</p>
2016-08-11T00:00:00ZAssessment of clinically related outcomes and biomarker analysis for translational integration in colorectal cancer (ACROBATICC): study protocol for a population-based, consecutive cohort of surgically treated colorectal cancers and resected colorectal liver metastasishttp://hdl.handle.net/1956/12539
Assessment of clinically related outcomes and biomarker analysis for translational integration in colorectal cancer (ACROBATICC): study protocol for a population-based, consecutive cohort of surgically treated colorectal cancers and resected colorectal liver metastasis
Søreide, Kjetil; Watson, Martin M; Lea, Dordi; Nordgård, Oddmund; Søreide, Jon Arne; Hagland, Hanne R
Journal article
<p>Background: More accurate predictive and prognostic biomarkers for patients with colorectal cancer (CRC) primaries or colorectal liver metastasis (CLM) are needed. Outside clinical trials, the translational integration of emerging pathways and novel techniques should facilitate exploration of biomarkers for improved staging and prognosis.</p>
<p>Methods: An observational study exploring predictive and prognostic biomarkers in a population-based, consecutive cohort of surgically treated colorectal cancers and resected colorectal liver metastases. Long-term outcomes will be cancer-specific survival, recurrence-free survival and overall survival at 5 years from diagnosis. Beyond routine clinicopathological and anthropometric characteristics and laboratory and biochemistry results, the project allows for additional blood samples and fresh-frozen tumour and normal tissue for investigation of circulating tumour cells (CTCs) and novel biomarkers (e.g. immune cells, microRNAs etc.). Tumour specimens will be investigated by immunohistochemistry in full slides. Extracted DNA/RNA will be analysed for genomic markers using specific PCR techniques and next-generation sequencing (NGS) panels. Flow cytometry will be used to characterise biomarkers in blood. Collaboration is open and welcomed, with particular interest in mutual opportunities for validation studies.</p>
<p>Status and perspectives: The project is ongoing and recruiting at an expected rate of 120&ndash;150 patients per year, since January 2013. A project on circulating tumour cells (CTCs) has commenced, with analysis being prepared. Investigating molecular classes beyond the TNM staging is under way, including characteristics of microsatellite instability (MSI) and elevated microsatellite alterations in selected tetranucleotides (EMAST). Hot spot panels for known mutations in CRC are being investigated using NGS. Immune-cell characteristics are being performed by IHC and flow cytometry in tumour and peripheral blood samples. The project has ethical approval (REK Helse Vest, #2012/742), is financially supported with a Ph.D.-Grant (EMAST project; Folke Hermansen Cancer Fund) and a CTC-project (Norwegian Research Council; O. Nordg&aring;rd). The ACROBATICC clinical and molecular biobank repository will serve as a long-term source for novel exploratory analysis and invite collaborators for mutual validation of promising biomarker results. The project aims to generate results that can help better discern prognostic groups in stage II/III cancers; explore prognostic and predictive biomarkers, and help detail the biology of colorectal liver metastasis for better patient selection and tailored treatment. The project is registered at http://www.ClinicalTrials.gov NCT01762813.</p>
2016-06-29T00:00:00ZA positive Real-Time Elastography (RTE) combined with a Prostate Cancer Gene 3 (PCA3) score above 35 convey a high probability of intermediate- or high-risk prostate cancer in patient admitted for primary prostate biopsyhttp://hdl.handle.net/1956/12536
A positive Real-Time Elastography (RTE) combined with a Prostate Cancer Gene 3 (PCA3) score above 35 convey a high probability of intermediate- or high-risk prostate cancer in patient admitted for primary prostate biopsy
Nygård, Yngve; Haukaas, Svein A.; Halvorsen, Ole J.; Gravdal, Karsten; Frugård, Jannicke; Akslen, Lars A.; Beisland, Christian
Journal article
<p>Background:
The standard of care in patients with suspected prostate cancer (PCa) is systematic prostate biopsies. This approach leads to unnecessary biopsies in patients without PCa and also to the detection of clinical insignificant PCa. Better tools are wanted. We have evaluated the performance of real-time elastography (RTE) combined with prostate cancer gene 3 (PCA3) in an initial biopsy setting with the goal of better identifying patients in need of prostate biopsies.</p>
<p>Methods:
127 patients were included in this study; three were excluded because of not measureable PCA3 score leading to 124 evaluable patients. A cut-off value of 35 was used for PCA3. All patients were examined with a Hitachi Preirus with an endfire probe for RTE, a maximum of five targeted biopsies were obtained from suspicious lesions detected by RTE. All patients then had a 10-core systematic biopsy performed by another urologist unaware of the RTE results. The study includes follow-up data for a minimum of three years; all available histopathological data are included in the analysis.</p>
<p>Results:
There was a significant difference in PCA3 score: 26.6 for benign disease, 73.6 for cancer patients (p &lt; 0.001). 70 patients (56 %) were diagnosed with prostate cancer in the study period, 21 (30 %) low-risk, 32 (46 %) intermediate-risk and 17 (24 %) high-risk. RTE and PCA3 were significant markers for predicting intermediate- and high-risk PCa (p = 0.001). The combination of RTE and PCA3 had a sensitivity of 96 % and a negative predictive value (NPV) of 90 % for the group of intermediate- and high-risk PCa together and a NPV for high-risk PCa of 100 %. If both parameters are positive there is a high probability of detecting intermediate- or high-risk PCa, if both parameters are negative there is only a small chance of missing prostate cancer with documented treatment benefit.</p>
<p>Conclusions:
RTE and PCA3 may be used as pre-biopsy examinations to reduce the number of prostate biopsies.</p>
2016-07-08T00:00:00ZThe Imaging and Cognition Genetics Conference 2011, ICG 2011: A Meeting of Mindshttp://hdl.handle.net/1956/12522
The Imaging and Cognition Genetics Conference 2011, ICG 2011: A Meeting of Minds
Le Hellard, Stephanie; Hanson, Isabel
Journal article
In June 2011, 70 researchers from the disciplines of cognitive science, genetics, psychology, psychiatry, neurobiology, and computer science gathered in Os, Norway, for the first Imaging and Cognition Genetics meeting. The aim of the conference was to discuss progress, enhance collaboration, and maximize the sharing of resources within this new field. In this Perspective, we summarize the major themes that emerged from ICG 2011. The first is the importance of defining cognitive and imaging phenotypes and endophenotypes suitable for genetic analysis. These can come from differential psychology, cognitive science, structural MRI, tractography, and functional imaging. The second theme is the emergence of new methods for the analysis of complex traits. These include advanced computational and statistical techniques for analyzing complex datasets, and new ways of interpreting data from genome-wide association studies, such as jointly evaluating the contribution of SNPs in specific genes and pathways rather than considering single SNPs in isolation. The final theme is the importance of establishing functional correlates of newly identified genetic variants.
2012-05-12T00:00:00ZMortality among retired offshore divers in Norwayhttp://hdl.handle.net/1956/12446
Mortality among retired offshore divers in Norway
Irgens, Ågot; Djurhuus, Rune; Grønning, Marit
Journal article
<p>Background: Health effects of diving have been observed in divers who have not experienced any diving related accidents. The aim of the study was to study total, and cause specific mortality, in Norwegian retired professional offshore divers.</p>
<p>Materials and methods: We carried out a mortality follow-up from 1997 to 2013 in a group of men, born 1930&ndash;1973. The diving cohort consisted of 386 male professional divers diving in the North Sea in the pioneer period from 1965 to 1990, of which 25 were dead. 1,467,769 Norwegian males were used as referents. This population was linked to the Norwegian Cause of Death Registry.</p>
<p>Results: Twenty five (6.5%) professional offshore divers had died. No differences were observed between divers and referents for overall mortality or for non-violent deaths, adjusted for year of birth.</p>
<p>Conclusions: In this cohort of retired North Sea divers, the mortality pattern did not differ from that of the expected mortality.</p>
2015-01-01T00:00:00ZComparing withdrawal and non-withdrawal of life-sustaining treatment among patients who died from strokehttp://hdl.handle.net/1956/12416
Comparing withdrawal and non-withdrawal of life-sustaining treatment among patients who died from stroke
Helvig, Eirik; Thomassen, Lars; Waje-Andreassen, Ulrike; Næss, Halvor
Journal article
<p>Background: In severe stroke, a decision to withdraw life-sustaining treatment is sometimes made in cooperation with the family. The aim of this study was to study the time from withdrawing life-sustaining treatment to death in patients with severe ischemic or hemorrhagic stroke.</p>
<p>Methods: In total, 2,506 patients with stroke admitted to Haukeland University Hospital between 2006 and 2011 were prospectively registered in the Bergen NORSTROKE database. Risk factors, stroke severity, etiology, and blood analyses were registered. Retrospectively, the patients&#39; records were examined to determine the number of days from withdrawing all life-sustaining treatment to death in patients who died from severe stroke during the hospital stay.</p>
<p>Results: Life-sustaining treatment was withheld in 50 patients with severe stroke. Median time to death after withdrawing life-sustaining treatment was 4 days, and a quarter lived at least 1 week (range =1&ndash;11 days). Cox regression analyses showed that short time from withdrawing life-sustaining treatment to death was associated with high age (Hazard ratio [HR] =1.05, P=0.07), male sex (HR =2.9, P=0.01), high C-reactive protein on admission (HR =1.01, P=0.001), and hemorrhagic stroke (versus ischemic stroke, HR =1.5, P=0.03).</p>
<p>Conclusion: One week after withdrawing life-sustaining treatment, a quarter of our patients with severe stroke remained alive. Short time to death was associated with high age, male sex, hemorrhagic stroke, and high C-reactive protein on admittance.</p>
2015-01-01T00:00:00ZClinically significant drug–drug interactions involving opioid analgesics used for pain treatment in patients with cancer: a systematic reviewhttp://hdl.handle.net/1956/12415
Clinically significant drug–drug interactions involving opioid analgesics used for pain treatment in patients with cancer: a systematic review
Kotlinska-Lemieszek, Aleksandra; Klepstad, Pål; Haugen, Dagny Faksvåg
Journal article
<p>Background:
Opioids are the most frequently used drugs to treat pain in cancer patients.
In some patients, however, opioids can cause adverse effects and drug–drug interactions.
No advice concerning the combination of opioids and other drugs is given in the current
European guidelines.</p>
<p>Objective:
To identify studies that report clinically significant drug–drug interactions involving
opioids used for pain treatment in adult cancer patients.</p>
<p>Design and data sources:
Systematic review with searches in Embase, MEDLINE, and
Cochrane Central Register of Controlled Trials from the start of the databases (Embase from
1980) through January 2014. In addition, reference lists of relevant full-text papers were hand-
searched.</p>
<p>Results:
Of 901 retrieved papers, 112 were considered as potentially eligible. After full-text
reading, 17 were included in the final analysis, together with 15 papers identified through hand-
searching of reference lists. All of the 32 included publications were case reports or case series.
Clinical manifestations of drug–drug interactions involving opioids were grouped as follows:
1) sedation and respiratory depression, 2) other central nervous system symptoms, 3) impairment
of pain control and/or opioid withdrawal, and 4) other symptoms. The most common mechanisms
eliciting drug–drug interactions were alteration of opioid metabolism by inhibiting the activity of
cytochrome P450 3A4 and pharmacodynamic interactions due to the combined effect on opioid,
dopaminergic, cholinergic, and serotonergic activity in the central nervous system.</p>
<p>Conclusion:
Evidence for drug–drug interactions associated with opioids used for pain treatment
in cancer patients is very limited. Still, the cases identified in this systematic review give some
important suggestions for clinical practice. Physicians prescribing opioids should recognize the
risk of drug–drug interactions and if possible avoid polypharmacy.</p>
2015-09-16T00:00:00ZUsing patient-reported outcome measures for improved decision-making in patients with gastrointestinal cancer – the last clinical frontier in surgical oncology?http://hdl.handle.net/1956/12397
Using patient-reported outcome measures for improved decision-making in patients with gastrointestinal cancer – the last clinical frontier in surgical oncology?
Søreide, Kjetil; Søreide, Annbjørg
Journal article
The genomic era has introduced concepts of “personalized medicine” and “targeted therapy” in the field of oncology. Medicine has become increasingly complex with a plethora of potential dilemmas in diagnosis, treatment, and management. The focus on classical outcomes for clinical decision-making is now increasingly being replaced by patient-reported outcome measures (PROMs). PROMs should increasingly now be in the center of patient-centered decision-making, based on valid, reliable, and clinically useful measures delivered directly by the patient to the caregiver. Surgeons’ ability to interpret and apply PROMs and quality of life results must improve by education and further research, and has an unreleased potential to contribute to a better understanding of the patients’ well-being. A number of caveats must be addressed before this can be brought to fruition; standardization for valid items; appropriate use of instruments; correct timing of the application; missing data handling, compliance, and respondent drop-outs are but a few issues to be addressed. Based on the apparent lack of use in both research and clinical work, it should call for an educational effort to address this among surgeons caring for patients with cancer.
2013-06-14T00:00:00ZAcute complications of spinal cord injurieshttp://hdl.handle.net/1956/12386
Acute complications of spinal cord injuries
Hagen, Ellen Merete
Journal article
The aim of this paper is to give an overview of acute complications of spinal cord injury (SCI). Along with motor and sensory deficits, instabilities of the cardiovascular, thermoregulatory and broncho-pulmonary system are common after a SCI. Disturbances of the urinary and gastrointestinal systems are typical as well as sexual dysfunction. Frequent complications of cervical and high thoracic SCI are neurogenic shock, bradyarrhythmias, hypotension, ectopic beats, abnormal temperature control and disturbance of sweating, vasodilatation and autonomic dysreflexia. Autonomic dysreflexia is an abrupt, uncontrolled sympathetic response, elicited by stimuli below the level of injury. The symptoms may be mild like skin rash or slight headache, but can cause severe hypertension, cerebral haemorrhage and death. All personnel caring for the patient should be able to recognize the symptoms and be able to intervene promptly. Disturbance of respiratory function are frequent in tetraplegia and a primary cause of both short and long-term morbidity and mortality is pulmonary complications. Due to physical inactivity and altered haemostasis, patients with SCI have a higher risk of venous thromboembolism and pressure ulcers. Spasticity and pain are frequent complications which need to be addressed. The psychological stress associated with SCI may lead to anxiety and depression. Knowledge of possible complications during the acute phase is important because they may be life threatening and/ or may lead to prolonged rehabilitation.
2015-01-01T00:00:00ZContinuous Local Intra-Arterial Nimodipine for the Treatment of Cerebral Vasospasmhttp://hdl.handle.net/1956/12332
Continuous Local Intra-Arterial Nimodipine for the Treatment of Cerebral Vasospasm
Logallo, Nicola; Bøthun, Marianne Lundervik; Guttormsen, Anne Berit; Holmaas, Gunhild; Kråkenes, Jostein; Thomassen, Lars; Svendsen, Frode; Helland, Christian Andre
Journal article
Vasospasm (VSP) is one of the major causes for prolonged neurologic deficit in patients
with aneurysmal subarachnoid hemorrhage. Few case series have reported about
continuous local intra-arterial nimodipine administration (CLINA) in refractory VSP.
We report our experience with CLINA in a patient with refractory cerebral VSP.
2015-01-01T00:00:00ZTreatment with a Peroxisome Proliferator-Activated Receptor agonist influences one-carbon metabolism and markers of B-vitamin status in ratshttp://hdl.handle.net/1956/12329
Treatment with a Peroxisome Proliferator-Activated Receptor agonist influences one-carbon metabolism and markers of B-vitamin status in rats
Lysne, Vegard
Master thesis
Introduction: Elevated plasma concentration of homocysteine (Hcy) has been considered as a candidate risk factor of cardiovascular disease (CVD), but lowering Hcy with B-vitamins has not been demonstrated to improve prognosis among CVD patients. It has thus been suggested that elevated Hcy serves only as a marker of underlying pathology, which prompts investigation into possible related mechanisms.
The choline oxidation pathway is directly linked to remethylation of Hcy to methionine, and increased systemic concentrations of metabolites along this pathway have previously been linked to major lifestyle diseases, including CVD. Choline-related remethylation of Hcy yields dimethylglycine (DMG). Notably, DMG has been demonstrated to be a strong predictor of CVD events and mortality, independent of other risk markers such as elevated Hcy levels.
The peroxisome proliferator-activated receptor (PPAR) α is a nuclear receptor and key regulator of energy metabolism which is activated by both dietary fatty acids and synthetic ligands such as fibrates. This receptor has recently been demonstrated to influence the genetic transcription of key enzymes of the choline oxidation pathway, and increased PPARα activity was thus suggested to be a possible underlying mechanism for the association between DMG and CVD.
Objective: The aim of the current study was to investigate the relationship between PPARα and one-carbon metabolism, with emphasis on the choline oxidation pathway. Most of the reactions in the metabolic pathways discussed depend on B-vitamins as cofactors, and hence we also assessed the associations between PPARα activation and systemic markers of B-vitamin status. A targeted metabolomic approach was implemented to investigate these relationships in a substudy of a long-term animal model.
Methods: During 50 weeks, 30 male Wistar rats were randomized to receive ad libitum of either a low fat control diet, a high fat (HF) diet or a HF diet supplemented with tetradecylthioacetic acid (TTA), a pan-PPAR agonist with pronounced affinity towards PPARα. At the end of the study, the animals were sacrificed under non-fasting conditions. Blood was drawn by cardiac puncture and urine collected directly from the urinary bladder. Metabolite concentrations were determined by gas and liquid chromatography coupled to tandem mass spectrometry. The groups were compared by one-way ANOVA, and planned
comparisons versus the control group were made for both intervention groups. Cohen’s d effect sizes were calculated and reported for all comparisons, and d > 0.8 was considered a large effect. As the results were not adjusted for multiple comparisons, p-values < 0.01 were considered statistically significant.
Results: When comparing TTA-treated animals to the control group, TTA-treated animals had statistically significantly higher plasma DMG (d=5.05), glycine (d=1.3), serine (d=1.99), cystathionine (d=1.52), nicotinamide (d=6.4), methylnicotinamide (d=4.05), methylmalonic acid (d=3.98) and pyridoxal (d= 2.73), whereas plasma riboflavin (d=-1.6) and flavin mononucleotide (d=-2.22) were lower. Urinary concentrations of DMG (d=1.98), sarcosine (d=1.16) and methylmalonic acid (d=1.89) were higher among TTA treated rats.
When comparing HF to the control group, no statistically significant differences were observed on either plasma or urinary concentrations of one-carbon metabolites or markers of B-vitamin status. However, the small sample size may have impeded statistical significance, as some of the differences were considered large. No differences were observed in urine according to dietary fat intake.
Conclusion: Long-term TTA treatment was associated with altered blood and urinary concentrations of one-carbon metabolites and markers of B-vitamin status in male Wistar rats. Particular large differences were observed for plasma DMG, NAM, mNAM and MMA, which were all higher among TTA-treated rats. Based on current and previous results, these effects are probably mainly mediated through PPARα. Our findings add to the evidence that one-carbon metabolism may be regulated by PPARs, and these candidate biomarkers of PPARα activity may prove to supply useful information which could help identifying human subgroups who will have clinical benefit of certain nutritional advice.
2014-06-15T00:00:00ZIschemic stroke and atherosclerosis at a young age. The Norwegian Stroke in the Young Studyhttp://hdl.handle.net/1956/12326
Ischemic stroke and atherosclerosis at a young age. The Norwegian Stroke in the Young Study
Fromm, Annette
Doctoral thesis
<p>Stroke risk and incidence increase exponentially with age. In Europe about one in
three strokes occurs before the age of 65 years, with severe socioeconomic
consequences on individual and society level. Despite improved diagnostic techniques
and increasing knowledge, in 30-50% of young stroke patients the cause of stroke
remains undetermined. However, due to the lack of one consistent definition for
“young stroke”, published data are inhomogeneous regarding patient age, stroke types
included and variables studied. It has been claimed that young stroke patients have a
favorable prognosis, including usually good recovery from neurological deficits, low
recurrence risk, a fair social prognosis, and favorable long-term outcome. Newer
follow-up investigations documented, however, high rates of stroke recurrence,
vascular co-morbidity and mortality. Further, increased rates of psychological
disorders, reduced health-related quality of life and impared social activity are
frequent long-term consequences. The underlying cause of stroke is related to
differing risk of recurrent cardiovascular events, being highest in patients with largeartery
atherosclerosis and cardioembolism. Hence, there is a need for systematic
investigation and data collection from well-defined young stroke populations aiming
to reveal the true cause of stroke, leading to right treatment of underlying conditions,
and to optimal and aggressive secondary prevention.</p>
<p>In the studies included in this thesis, we aimed to compare stroke characteristics in
young ischemic stroke patients to older patient populations, and to controls free of
cardiovascular disease. Data were obtained from 1217 ischemic stroke patients
admitted to Haukeland University Hospital between 2006 and 2009 (the Bergen
NORSTROKE study), and from 150 patients aged 15-60 years and 84 controls
included in the Norwegian Stroke in the Young Study (NOR-SYS) between 2010 and
2012. Patients &lt;50 years represented 8% of the NORSTROKE population.
Undetermined cause of stroke was the most frequent subtype of stroke classified
according to TOAST criteria in NORSTROKE and NOR-SYS. Of determined causes, non-arrhythmic cardioembolism, small artery occlusion and cervical artery dissection
were the most frequent diagnoses among younger patients, while cardioembolism due
to arrhythmia was the most frequent cause of stroke among older patients. Risk factor
burden increased with age, and patients of all investigated age and sex subgroups had
a higher risk factor burden than controls. Of the risk factors investigated,
hypertension, dyslipidemia, smoking, overweight and family history of cardiovascular
disease were most frequent. Carotid Intima-media thickness (cIMT), a surrogate
marker of atherosclerosis, was measured by ultrasonography in the NOR-SYS
population, and performed in the common carotid artery (CCA), the bifurcation (BIF)
and the internal carotid artery (ICA). Increased cIMT was associated with age and
prevalent vascular risk factors. The overall cIMT difference between patients and
controls was 12% in CCA, 17% in BIF and 29% in ICA. Mean cIMT was higher
compared to controls in patients with large-artery atherosclerosis, small artery
occlusion, and stroke of undetermined cause.</p>
<p>Our data add new information to our knowledge about young stroke patients
concerning etiology, risk factors, and the prevalence of clinical and subclinical carotid
artery disease. They support the conclusions drawn in previous studies regarding the
varying impact of different risk factors on cIMT development dependent on age and
sex. We find ICA to be the carotid segment distinctly associated with incident stroke,
related to a family history of cardiovascular disease among young patients, and related
to an increasing risk factor burden with increasing age. We further find that small
artery occlusion and stroke of undetermined etiology represent stroke subtypes which
hide a considerable number of patients suffering from atherosclerotic arterial disease
in our cohort. Young stroke patients require extensive investigation with the purpose
to detect and treat prevalent vascular disease and risk factors aggressively, to slow the
progression of atherosclerotic disease, and to prevent future vascular events and
subsequent disability, cognitive decline and death.</p>
2014-01-31T00:00:00ZComparison between Ischemic Stroke Patients <50 Years and ≥50 Years Admitted to a Single Centre: The Bergen Stroke Studyhttp://hdl.handle.net/1956/12325
Comparison between Ischemic Stroke Patients <50 Years and ≥50 Years Admitted to a Single Centre: The Bergen Stroke Study
Fromm, Annette; Waje-Andreassen, Ulrike; Thomassen, Lars; Næss, Halvor
Journal article
<p>Introduction: Young adults are likely to differ from old patients concerning cerebral infarction.</p>
<p>Methods: We compared
characteristics of patients aged under and above 50 years, admitted to the Department of Neurology with cerebral infarction
between 2006 and 2009, based on prospective registration. Investigation followed one common protocol for both groups.</p>
<p>Results and Discussion: One hundred patients (8.2%) were <50 years old, and the proportion of males was higher in this group (72%
versus 55.8%, P = .002). Young stroke patients are more often current smokers (44.1% versus 23.6%, P < .001). Common causes
for stroke in the young were cervical artery dissection (18% versus 0.6%, P < .001) and cardiac embolism due to disorders other
than atrial arrhythmias (18% versus 5.5%, P < .001). Among the old, atrial fibrillation and flutter dominated (29.1% versus
5%, P < .001). Stroke severity and location did not differ. Old patients more often suffered from pneumonia (10.6% versus
2%, P < .003) and urinary tract infection (14.6% versus 2%, P = .001).</p>
<p>Conclusions: Males dominate, and current smoking
is more common in the young. Cervical artery dissection and nonarrhythmic heart disorders are frequent causes among young
patients, while traditional risk factors dominate the old. Stroke severity is similar, but old patients seem more exposed for infectious
complications.</p>
2011-01-01T00:00:00ZForskningsveiledning - en av de essensielle faktorene på «veien til doktorgrad»http://hdl.handle.net/1956/12291
Forskningsveiledning - en av de essensielle faktorene på «veien til doktorgrad»
Lied, Gülen Arslan; Chen, Jian; Reikvam, Håkon
Journal article
The journey to finish a PhD thesis is a long race, and several factors may play important roles in this process. A good working relationship between the supervisor and the candidate is an essential component for achieving a successful outcome. It is, therefore, essential to identify the factors that affect the PhD program, including support provided from supervisors, and counselling practice and co-work in the scientific community. It is also important to identify key characteristics of both the candidates and the supervisors and to investigate how they collaborate. With this purpose, we performed a survey during the fall semester of 2012 at an institute at the Faculty of Medicine and Dentistry, University of Bergen (UiB). Thirteen main supervisors and co-supervisors answered a structured questionnaire. The results demonstrated that the supervisors had on average a long guidance experience (11 years), while the candidates spent a short time to complete the PhD program (Mean: 3.5 years). The preferred form of counselling was a meeting between the supervisor and candidate, and all supervisors had regular contact with their fellows. Moreover, the dropout rate of PhD students was very low. Characteristics of a good PhD student highlighted by supervisors were commitment, high work capacity, teamwork ability and independence. The survey indicates that supervisors view guidance as one of their key tasks, often in addition to their own research and clinical work. For candidates, it is important to be associated with an active scientific environment to increase both the quality and efficiency of the learning process.; Veien til doktorgraden er et langt løp, og flere faktorer kan spille en betydelig rolle i løpet av denne prosessen. Et godt fungerende forhold mellom veileder og kandidat er en essensiell faktor for å oppnå et vellykket resultat. Derfor er det viktig å kartlegge faktorer som påvirker ph.d.-utdanningen – hvilken støtte man får fra veileder/veiledere og hvordan veiledningspraksis er og fungerer i det vitenskapelige miljøet. Det er også viktig å kunne identifisere viktige egenskaper hos både kandidat og veileder og kunne si noe om hvordan de fungerer sammen.
Med dette formålet utførte vi en undersøkelse høstsemesteret 2012 ved et institutt ved Det medisinsk-odontologiske fakultet ved Universitetet i Bergen (UiB). Tretten hoved- og biveiledere besvarte et strukturert spørreskjema.
Resultatene viste at veilederne hadde i gjennomsnitt 11 års veiledningserfaring. Kandidatene brukte i gjennomsnitt 3,5 år på ph.d.-utdanningen. Den mest foretrukne veiledningsformen for kandidater og veiledere var avtalte møter. Alle veilederne hadde regelmessig kontakt med sine stipendiater. Videre var frafallet av ph.d.-studenter svært lav. Egenskaper hos en god stipendiat som ble fremhevet av veiledere var engasjement, stor arbeidskapasitet, samarbeidsevne og selvstendighet.
Undersøkelsen indikerer at veilederne tar veiledning som en sentral arbeidsoppgave, ofte i tillegg til egen forskning og klinisk arbeid. For kandidater er det viktig å være tilknyttet et aktiv vitenskapelig miljø for å øke både kvaliteten og effektiviteten av læringsprosessen.
2013-01-01T00:00:00ZAttention deficit/hyperactivity disorder and occurrence of epilepsy, interictal epileptiform discharges and two years follow-up in childrenhttp://hdl.handle.net/1956/12229
Attention deficit/hyperactivity disorder and occurrence of epilepsy, interictal epileptiform discharges and two years follow-up in children
Socanski, Dobrinko
Doctoral thesis
<p>The detection and treatment of both attention deficit/hyperactivity disorder (ADHD) and
epilepsy in young patients are challenging. In some cases, the occurrence of interictal
epileptiform discharges (IEDs) flowers the picture, and some clinicians are reluctant to use
methylphenidate (MPH) in such cases. Many studies discussed ADHD in children with
epilepsy, but only a few investigated relationships between ADHD, IEDs and epilepsy in
children with ADHD. It is unclear whether it is safe to use MPH in children with ADHD and
comorbid epilepsy and/or IEDs.
<p>Aims: We investigated the occurrence of epilepsy and IEDs on awake EEG at baseline in a
large sample of children diagnosed with ADHD. Finally, we studied whether the use of MPH
would increase the risk for epilepsy in a 2 year prospective, and whether IEDs at baseline
influence the occurrence of epileptic seizures (SZs), the use of MPH and the use of
antiepileptic drugs (AEDs).
<p>Methods: This is a retrospective chart review of all children aged between 6-14 years
diagnosed with ADHD over a 6 year period (2000-2005). First, we examined the prevalence
and characteristics of epilepsy in children with ADHD and compared it with a general
pediatric population, and initial use of MPH in cases with and without epilepsy. Second, we
investigated the occurrence of IED on awake EEG at baseline in all children who performed a
routine EEG. The clinical characteristics of ADHD children (ADHD inattentive subtype,
comorbidities) in cases with and without IEDs were analyzed. Finally, we compared the
patients with IEDs (IEDs group) with matched controls (age and gender) without IEDs (non-
IEDs group) in a 2 year follow-up. We wanted to examine the use of MPH (initial use, positive
response, maintenance on MPH), the use of AEDs, and whether it was safe to use MPH in
cases with IEDs (seizure risk) during the first 2 years of treatment. A control EEG was carried
out in the IEDs group.
<p>Results: We found that 2.3 % of children (N=607) had epilepsy. This is significantly higher
than in the general pediatric population (0.5%). In all children, the diagnosis of epilepsy was
made before ADHD diagnosis. We were able to carry out baseline EEG in 517 cases and IEDs
were found in 39 (7.5%), or in 27 (5.4%), if patients with previous epilepsy were excluded.
When we compare this rate with rates of IEDs reported in healthy children, it is unclear
whether any differences exist. The cases with IEDs more often had inattentive type of ADHD
regardless of previous history of epilepsy. Of the children with IEDs, only children with
previous difficult to treat epilepsy developed SZs during the 2 year follow-up, but without
any change in SZ frequency. The groups with and without IEDs did not have significant
differences in the use of MPH. Some cases from the IEDs group temporarily used AEDs
because of diagnostic uncertainties.
<p>Conclusions:
Epilepsy and IEDs occur more often in children with ADHD compared to the general pediatric
population and healthy children. The groups with and without IEDs had similar use of MPH
during the two 2 year follow-up. The occurrence of IEDs at baseline was not associated with
an increased SZ risk during the 2 year follow-up despite the use of MPH.
2016-06-15T00:00:00ZOlfactory dysfunction in chronic stroke patientshttp://hdl.handle.net/1956/12220
Olfactory dysfunction in chronic stroke patients
Wehling, Eike; Næss, Halvor; Wollschlaeger, Daniel; Hofstad, Håkon; Bramerson, Annika; Bende, Mats; Nordin, Steven
Journal article
Background The aim of the study was to investigate odor identification performance in patients one year after hospital admittance due to stroke. Predictors for olfactory dysfunction were investigated as well as self-reported olfactory function and pleasantness of olfactory items. Methods A 1-year prospective study was performed. Stroke location, classification and comorbidities were registered at hospital admission. One year after admission, olfactory function was assessed using standardized olfactory methods (screening for loss of detection sensitivity and an odor identification test). A group of matched controls was derived from a population-based study to compare odor identification performance between groups. Patients were asked for their personal judgment regarding their olfactory function and pleasantness of odorous items. In addition, global cognitive function and symptoms of depression were assessed. Results A total of 78 patients were enrolled (46 males, 32 females; mean age 68 years) of which 28.2 % exhibited reduced olfactory function (hyposmia) and 15.4 % exhibited loss of olfactory function (10.3 % functional anosmia, 5.1 % complete anosmia). Patients showed significantly lower olfactory performance compared to age- and sex-mated matched controls. Predictors of impaired olfactory function were age and NIHSS score. Self-reports indicated no significant differences between patients with normal olfactory function and those with reduced function. Yet, patients having an olfactory dysfunction rated odorous items as significantly less pleasant compared to patients without dysfunction. Conclusions Olfactory dysfunction seems to occur frequently after stoke even one year after initial admission. The deficits seem to relate to hyposmia and functional anosmia, and less to a complete loss of smell sensitivity.
2015-10-12T00:00:00ZMolecular dysfunction associated with the human mitochondrial 3302A>G mutation in the MTTL1 (mt-tRNA Leu(UUR))) genehttp://hdl.handle.net/1956/12109
Molecular dysfunction associated with the human mitochondrial 3302A>G mutation in the MTTL1 (mt-tRNA Leu(UUR))) gene
Maniura-Weber, Katharina; Helm, Mark; Engemann, Katrin; Eckertz, Sabrina; Möllers, Myriam; Schauen, Matthias; Haryapetyan, Armine; Kleist-Retzow, Jürgen-Christoph von; Lightowlers, Robert N.; Bindoff, Laurence; Wiesner, Rudolf J.
Journal article
The gene encoding mt-tRNALeu(UUR), MT-TL1, is a hotspot for pathogenic mtDNA mutations. Amongst the first to be described was the 3302A>G transition which resulted in a substantial accumulation in patient muscle of RNA19, an unprocessed RNA intermediate including mt-16S rRNA, mt-tRNALeu(UUR) and MTND1. We have now been able to further assess the molecular aetiology associated with 3302A>G in transmitochondrial cybrids. Increased steady-state levels of RNA19 was confirmed, although not to the levels previously reported in muscle. This data was consistent with an increase in RNA19 stability. The mutation resulted in decreased mt-tRNALeu(UUR) levels, but its stability was unchanged, consistent with a defect in RNA19 processing responsible for low tRNA levels. A partial defect in aminoacylation was also identified, potentially caused by an alteration in tRNA structure. These deficiencies lead to a severe defect in respiration in the transmitochondrial cybrids, consistent with the profound mitochondrial disorder originally associated with this mutation.
2006-11-27T00:00:00ZFamily history in young and middle-aged acute ischemic stroke patients. The Norwegian Stroke in the Young Studyhttp://hdl.handle.net/1956/12079
Family history in young and middle-aged acute ischemic stroke patients. The Norwegian Stroke in the Young Study
Øygarden, Halvor
Doctoral thesis
<p>Cardiovascular disease (CVD), including stroke, coronary heart disease (CHD) and peripheral artery disease, is the leading cause of death and disability in the western world. CVD is influenced by genetic and lifestyle factors. Knowledge about heredity is well documented for CHD. However, the influence of a positive family history (FH) on stroke is far less documented. </p>
<p>The studies included in this thesis therefore aim to quantify and evaluate a detailed FH of CVD in a young ischemic stroke population with a special regard to sex differences. Further, we aimed to verify the patient reported family history by comparison with parental reports, and to find factors associated with best accuracy of the patient reported FH. In addition we aimed to analyze if a positive FH of CVD is associated with intima-media thickness (IMT) and plaque measurements, performed at standardized sites in the carotid arteries. </p>
<p>A total of 59% of our patients reported ischemic CVD events among their first degree family members. Females were three times more likely to report a positive FH than males and knowledge of FH was higher in relatives with a female than male linkage. Detailed knowledge on FH was better for CHD than for stroke. The FH reported from patients were in good concordance with parental reports, but with a slightly decreased accuracy from patients aged over 45 years. FH of stroke was associated with higher internal carotid IMT in young ischemic stroke patients. The association was strong for young patients, and absent in the highest age group from 50-60 years. </p>
<p>In conclusion, data presented in this thesis, add new information to the field of young stroke by a detailed FH of CVD and detailed ultrasound diagnostics of the carotid arteries. Thorough diagnostics after ischemic stroke and the history of ischemic CVD events in first degree family members should be basic requirements for future genetic research. </p>
2016-04-08T00:00:00ZPersistence of a pKPN3-like CTX-M-15-encoding IncFIIK plasmid in a Klebsiella pneumonia ST17 host during two years of intestinal colonizationhttp://hdl.handle.net/1956/12058
Persistence of a pKPN3-like CTX-M-15-encoding IncFIIK plasmid in a Klebsiella pneumonia ST17 host during two years of intestinal colonization
Löhr, Iren Høyland; Hülter, Nils Fredrik; Bernhoff, Eva; Johnsen, Pål Jarle; Sundsfjord, Arnfinn; Naseer, Mohammed Umaer
Journal article
Objectives. To characterize the CTX-M-15-encoding plasmid in a Klebsiella pneumoniae ST17 strain, responsible for an outbreak at a Norwegian neonatal intensive care unit and subsequent colonization of affected children for up to two years. To identify plasmid-mediated features relevant for the outbreak dynamics, and to investigate the plasmids capability of horizontal transfer, its segregational stability and plasmid-mediated fitness costs.
Methods. Plasmid profiling was performed by S1-nuclease PFGE, PCR-based replicon typing and Southern blot-hybridization. The complete sequence of the CTX-M-15-encoding plasmid was obtained by 454 sequencing. Plasmid self-transferability was investigated by broth- and filter mating, segregational stability was explored by serial passage, and plasmid-conferred fitness costs were examined in pairwise head-to-head competitions and by growth rate comparisons.
Results. CTX-M-15 was encoded by a ~180 kb IncFIIK plasmid in K. pneumoniae ST17. S1-nuclease PFGE profiles of the first and the last CTX-M-15-producing K. pneumoniae isolates, recovered from the four children colonized the longest, suggested that the plasmid was stably maintained during intestinal carriage of up to two years. The DNA sequence of the pKPN3-like plasmid, pKp848CTX, uncovered a Tn3-like antibiotic resistance region and multiple heavy metal- and thermoresistance determinants. Plasmid pKp848CTX could not be transferred to Escherichia coli in vitro and we found no evidence to support horizontal plasmid transfer in vivo. Segregational plasmid loss ranging from 0.83% to 17.5% was demonstrated in evolved populations in vitro, but only minor fitness costs were associated with plasmid-carriage.
Conclusions. Plasmid pKp848CTX encodes phenotypic traits, which may have had an impact on the fitness and survival of the K. pneumoniae ST17 strain in the outbreak setting. The antibiotic resistance plasmid pKp848CTX was stably maintained during two years of intestinal colonization, conferring negligible fitness cost to its host, and thus seem well adapted to its K. pneumoniae host.
2015-03-04T00:00:00ZIn vitro-stimulated IL-6 monocyte secretion and in vivo peripheral blood T lymphocyte activation uniquely predicted 15-year survival in patients with head and neck squamous cell carcinomahttp://hdl.handle.net/1956/12044
In vitro-stimulated IL-6 monocyte secretion and in vivo peripheral blood T lymphocyte activation uniquely predicted 15-year survival in patients with head and neck squamous cell carcinoma
Aarstad, Helene Hersvik; Vintermyr, Olav Karsten; Ulvestad, Elling; Kross, Kenneth Wilfried; Heimdal, John-Helge; Aarstad, Hans Jørgen
Journal article
The study was performed in order to determine whether peripheral blood monocyte in vitro function, and lymphocyte in vivo activation at diagnosis, was associated with HPV tumor infection status and 15-year survival in head and neck squamous cell carcinoma (HNSCC) patients. Sixty-five patients from a consecutive cohort of newly diagnosed HNSCCs, together with 18 control patients, were included in the study. Monocyte responsiveness was assessed by measuring monocyte in vitro interleukin (IL)-6 secretions after 24 hours of LPS stimulation in cultures with a serum-free medium. T lymphocyte activation was determined as the fraction of CD71-positive cells on CD3-positive cells by flow cytometry, whereas HPV infection was determined by PCR on formalin-fixed paraffin-embedded (FFPE) tumor tissue. Disease-specific survivals and overall survivals were determined 15 years following inclusion. HPV-positive HNSCC patients had a lower monocyte LPS-stimulated IL-6 response. A high LPS-stimulated monocyte IL-6 response predicted a decreased survival rate (P=0.019). A high percentage of CD71-positive T lymphocytes also predicted an impaired prognosis (P=0.021). The predictive power of IL-6 monocyte LPS-stimulated responses was retained when adjusted for age, gender and TNM stage of the patients. The monocyte and T lymphocyte survival predictions were independent of each other. The survival was particularly low with a combined high activated monocyte and T lymphocyte status. In a multivariate analysis, IL-6 secretion and the percentage of CD71-positive T lymphocytes both uniquely predicted survival independent of HPV infection status. It is postulated that the natural and adaptive immune systems are separately and additionally linked to the clinical aggressiveness of HNSCCs.
2015-06-16T00:00:00ZDietary guidance normalizes large intestinal endocrine cell densities in patients with irritable bowel syndromehttp://hdl.handle.net/1956/12011
Dietary guidance normalizes large intestinal endocrine cell densities in patients with irritable bowel syndrome
Mazzawi, Tarek; Hausken, Trygve; Gundersen, Doris Irene; El-Salhy, Magdy
Journal article
<p>Background/Objectives: To determine the large intestinal endocrine cell types affected following dietary guidance in patients with irritable bowel syndrome (IBS).</p>
<p>Subjects/Methods: The study included 13 IBS patients and 13 control subjects. The patients received three sessions of individualized dietary guidance. Both the control subjects and the patients were scheduled for colonoscopies at baseline and again for the patients at 3–9 months after dietary guidance. Biopsy samples were taken from the colon and rectum and were immunostained for all types of large intestinal endocrine cells. The endocrine cells were quantified using computerized image analysis.</p>
<p>Results: The daily total consumption (mean±s.e.m. values) of fruits and vegetables rich in FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) decreased significantly from 16.2±5.3 g before receiving dietary guidance to 9.2±3.2 g after receiving dietary guidance (P=0.02). In the total colon, the densities of serotonin cells were 46.8±8.9, 10.5±2.1 and 22.6±3.2 cells/mm2 in control subjects and in IBS patients before and after receiving dietary guidance, respectively (P=0.007); the corresponding densities of peptide YY cells were 11.6±1.8, 10.8±1.7 and 16.8±2.1 cells/mm2, respectively (P=0.06). The cell densities for both serotonin and peptide YY did not change significantly in the rectum. The densities of somatostatin cells in the rectum were 13.5±3.0, 13.2±3.0, and 22.3±3.2 cells/mm2 for control subjects and for IBS patients before and after receiving dietary guidance, respectively (P=0.01).</p>
<p>Conclusions: The densities of the large intestinal endocrine cells tend to normalize following dietary guidance that may have contributed to the improvement of the patients with IBS symptoms.</p>
2015-11-25T00:00:00ZDefault-mode network functional connectivity is closely related to metabolic activityhttp://hdl.handle.net/1956/12005
Default-mode network functional connectivity is closely related to metabolic activity
Passow, Susanne; Specht, Karsten; Adamsen, Tom Christian; Biermann, Martin; Brekke, Njål; Craig-Craven, Alexander Richard; Ersland, Lars; Grüner, Renate; Kleven-Madsen, Nina; Kvernenes, Ole Heine; Schwarzlmüller, Thomas; Olesen, Rasmus Aamand; Hugdahl, Kenneth
Journal article
Over the last decade, the brain's default-mode network (DMN) and its function has attracted a lot of attention in the field of neuroscience. However, the exact underlying mechanisms of DMN functional connectivity, or more specifically, the blood-oxygen level-dependent (BOLD) signal, are still incompletely understood. In the present study, we combined 2-deoxy-2-[18F]fluoroglucose positron emission tomography (FDG-PET), proton magnetic resonance spectroscopy (1H-MRS), and resting-state functional magnetic resonance imaging (rs-fMRI) to investigate more directly the association between local glucose consumption, local glutamatergic neurotransmission and DMN functional connectivity during rest. The results of the correlation analyzes using the dorsal posterior cingulate cortex (dPCC) as seed region showed spatial similarities between fluctuations in FDG-uptake and fluctuations in BOLD signal. More specifically, in both modalities the same DMN areas in the inferior parietal lobe, angular gyrus, precuneus, middle, and medial frontal gyrus were positively correlated with the dPCC. Furthermore, we could demonstrate that local glucose consumption in the medial frontal gyrus, PCC and left angular gyrus was associated with functional connectivity within the DMN. We did not, however, find a relationship between glutamatergic neurotransmission and functional connectivity. In line with very recent findings, our results lend further support for a close association between local metabolic activity and functional connectivity and provide further insights towards a better understanding of the underlying mechanism of the BOLD signal.
2015-06-01T00:00:00ZA transneuronal analysis of the olivocochlear and the middle ear muscle reflex pathwayshttp://hdl.handle.net/1956/11988
A transneuronal analysis of the olivocochlear and the middle ear muscle reflex pathways
Mukerji, Sudeep
Doctoral thesis
<p>Backgroun. In the auditory brainstem of mammals, there are two main descending reflex systems to the auditory system; The middle ear muscle reflex and the olivocochlear reflex. The two middle ear muscles participating in the middle ear muscle reflex are the stapedius and the tensor tympani. In man, the stapedius is known to react to strong low frequency acoustic stimulation, enacting forces perpendicular to the stapes superstructure, increasing middle ear impedance and reducing the intensity of acoustic energy arriving at the cochlea of the inner ear. Unlike the stapedius, the tensor tympani muscle has been proven to contract in response to self-generated noise such as chewing, swallowing and other non-auditory stimuli. The first theories on tensor tympani function were created by the a 16th Century Italian anatomist and scientist called Hieronymous Fabricius (1533-1619). He was the first to allude to both an auditory and non-auditory role of the tensor tympani muscle in humans. Since his work, many theories have been created founded on an evolving ability to analyze the components of the middle ear reflex pathways of the brainstem using various labeling techniques. It is now known that transduction of sound happens in the cochlea, causing an action potential that is sent along the auditory nerve to the cochlear nucleus in the brainstem. The cochlear nucleus is the first relay station for all ascending sound information originating in the ear. Unknown interneurons in the ventral cochlear nucleus then spread either directly or indirectly to the multiple middle ear muscle motoneurons located elsewhere in the brainstem. These motoneurons provide efferent innervation to the stapedius and the tensor tympani. There are many interesting differences among species in the acoustic thresholds for contraction of the middle ear muscles, which may be a reflection of underlying anatomical and physiological differences such as the number of tensor tympani muscle motoneurons. The goal of one of our research studies was to investigate the quantity, location and morphological characteristics of the tensor tympani motoneurons in the mouse model. Although the ascending and descending limbs of these reflex pathways have been described, the identity of the reflex interneurons within the reflex pathway is still unknown, as are the sources of modulatory inputs to these pathways. Olivocochlear neurons participate in the olivocochlear reflex pathway. They react to acoustic stimulation and provide descending input that controls auditory processing in the cochlea. As in the middle ear muscle reflex, the identities of these neurons in the pathways providing inputs to olivocochlear neurons are also incompletely understood and similar labeling techniques were used to further study these interneurons. Furthermore, we relate our findings to the unpublished results off recent experiments that used infrared light as a means of stimulating the auditory brainstem as a possible technology in future clinical applications of brainstem implants. </p>
<p>Materials and methods. This work consists primarily of four papers of which two are based on research that focuses on the anatomical geography (and postulated function) of the middle ear and the olivocochlear reflex pathways. The animal models in each investigation were mice and guinea pig. For the tensor tympani muscle reflex experiments, we used the chemical trans-synaptic tracer called Fluorogold to retrogradely label cell bodies and their dendrites in mice. For the olivocochlear reflex experiments, we also used a retrograde transneuronal tracer but in the form of a pseudorabies virus (Bartha strain, expressing green fluorescent protein) to label neurons and their input in guinea pigs. These animal models have become the most common subjects for auditory and neuroscience research based on many factors, both biological and practical. The mouse and guinea pig were chosen because of the large availability of genetically altered strains in neuroscience research. Their relatively short lifespan renders them preferable for studies on the effects of aging. Furthermore, the very high frequency range of the hearing in mice vs. the low-frequency effects of middle ear muscle contraction makes it interesting to speculate on the functional roles of middle ear muscles in this species. The aim of the scientific papers was to provide an overview of the middle ear muscle reflex anatomy and physiology, to present new data on the middle ear muscle reflex anatomy and physiology, to describe the clinical implications of our research and to dedicate some attention to the historical efforts of research on the middle ear muscles, especially the tensor tympani. The latter was achieved by studying the original theories presented on tensor tympani function postulated by a renowned Italian anatomist/scientist named Hieronymous Fabricius (1533-1619). These theories, translated from Latin, were analyzed from his book “De Visione, Voce et Auditu” (The vision, voice and hearing) first published in 1600 and access to which was gained with scheduled permission from the Harvard Center for Rare Books, Cambridge (Massachusetts, USA). </p>
<p>Results and conclusions. After injections of Fluorogold into the tensor tympani muscle, a column of labeled tensor tympani motoneurons (TTMNs) was identified ventro-lateral to the ipsilateral trigeminal nucleus. The labeled TTMNs were classified according to their morphological characteristics into three subtypes: “octopus-like”, “fusiform” and “stellate”, suggesting underlying differences in function. All three subtypes formed sparsely branched and radiating dendrites, some longer than 600 μm. Dendrites were longest and most numerous in the dorso-medial direction, stretching into non-auditory regions of the brainstem. The long dendrites and the various subtypes of TTMNs support the idea that contraction of the tensor tympani muscle can be secondary to multiple non-auditory inputs. Our findings agree with past experiments showing that the labeled TTMNs were found just outside the trigeminal motor nucleus, probably forming part of a separate “tensor tympani motor nucleus of V”. This separate nucleus was distinct from the trigeminal motor nucleus in term of cellular composition and orientation. To explore the olivocochlear pathways, the retrograde transneuronal tracer pseudorabies virus (Bartha strain, expressing green fluorescent protein) was used successfully to label neurons and their inputs in guinea pigs. Labeling of olivocochlear neurons started on the first day after injection into the cochlea. On the second day (and for longer survival times), transneuronal labeling spread to the cochlear nucleus, inferior colliculus, and other brainstem areas. There was a relationship between the numbers of these transneuronally labeled neurons and the number of labeled medial olivocochlear neurons, implying that the spread of labeling proceeds predominantly via synapses on the medial olivocochlear neurons. In the cochlear nucleus, the transneuronally labeled neurons were classified as “multipolar” cells including the subtype known as “planar” cells. In the central nucleus of the inferior colliculus, transneuronally labeled neurons were of two principal types: neurons with disc-shaped dendritic fields and neurons with dendrites in a stellate pattern. Transneuronal labeling was also observed in pyramidal cells in the auditory cortex and in centers not typically associated with the auditory pathway such as the pontine reticular formation, subcoerulean nucleus, and the pontine dorsal raphe. These data presents us more information on the identity of neurons providing input to auditory neurons, which are located in auditory as well as non-auditory centers. Additionally, we learnt from translated written accounts that Fabricius was a pioneer in approaching anatomy from a structure-function relationship and that he was an active proponent for improving the learning environment for students. The writings of Fabricius on the middle ear also provided the foundation for modern ideas on the role of the tensor tympani in mammals. He was also the first to propose a non-auditory function to this middle ear muscle.</p>
2016-04-29T00:00:00ZThe Norwegian preeclampsia family cohort study: a new resource for investigating genetic aspects and heritability of preeclampsia and related phenotypeshttp://hdl.handle.net/1956/11977
The Norwegian preeclampsia family cohort study: a new resource for investigating genetic aspects and heritability of preeclampsia and related phenotypes
Roten, Linda T; Thomsen, Liv C V; Gundersen, Astrid S; Fenstad, Mona H; Odland, Maria L; Strand, Kristin M; Solberg, Per; Tappert, Christian; Araya, Elisabeth; Bærheim, Gunhild; Lyslo, Ingvill; Tollaksen, Kjersti; Bjørge, Line; Austgulen, Rigmor
Journal article
Background. Preeclampsia is a major pregnancy complication without curative treatment available. A Norwegian Preeclampsia Family Cohort was established to provide a new resource for genetic and molecular studies aiming to improve the understanding of the complex pathophysiology of preeclampsia. Methods. Participants were recruited from five Norwegian hospitals after diagnoses of preeclampsia registered in the Medical birth registry of Norway were verified according to the study’s inclusion criteria. Detailed obstetric information and information on personal and family disease history focusing on cardiovascular health was collected. At attendance anthropometric measurements were registered and blood samples were drawn. The software package SPSS 19.0 for Windows was used to compute descriptive statistics such as mean and SD. P-values were computed based on t-test statistics for normally distributed variables. Nonparametrical methods (chi square) were used for categorical variables. Results. A cohort consisting of 496 participants (355 females and 141 males) representing 137 families with increased occurrence of preeclampsia has been established, and blood samples are available for 477 participants. Descriptive analyses showed that about 60 % of the index women’s pregnancies with birth data registered were preeclamptic according to modern diagnosis criteria. We also found that about 41 % of the index women experienced more than one preeclamptic pregnancy. In addition, the descriptive analyses confirmed that preeclamptic pregnancies are more often accompanied with delivery complications. Conclusion. The data and biological samples collected in this Norwegian Preeclampsia Family Cohort will provide an important basis for future research. Identification of preeclampsia susceptibility genes and new biomarkers may contribute to more efficient strategies to identify mothers “at risk” and contribute to development of novel preventative therapies.
2015-12-01T00:00:00ZRole of integrin α11 in oral carcinogenesis. In vitro and in vivo studieshttp://hdl.handle.net/1956/11974
Role of integrin α11 in oral carcinogenesis. In vitro and in vivo studies
Parajuli, Himalaya
Doctoral thesis
<p>Cancer research has provided evidence for several advanced and better ways of treatment, helping the community for a better living. Nevertheless, for head and neck cancer there is still a long way to go for achieving an earlier and a more precise diagnosis and a better, more targeted and less toxic treatment plan, which would ensure a longer survival with a better quality of life for the patients. Research has shown, in the recent years that the tumour microenvironment is an important cluster of players for tumour progression and response to therapy, which can be used for patient stratification and for a better, more efficient therapy. </p>
<p>Head and neck cancer is the eighth most common type of human cancer, squamous cell carcinoma being the most common variant. The number of head and neck cancer cases is increasing worldwide, but particularly in the low-income countries, and mainly for the cases limited to the oral cavity. As an oral cancer lesion progresses, directly or indirectly the environment around is affected, which either promote or try to resist the growth of the tumour. Nevertheless, the specific role of the various components of microenvironment and their importance for tumour prognosis and treatment are still not fully understood. The aim of this study was to determine the expression pattern and the role of integrin a11, a collagen receptor recently associated with the carcinoma associated fibroblast (CAF) phenotype, in oral cancer progression, in order to determine its potential as a biomarker and as a key player for oral carcinogenesis. </p>
<p>The expression pattern of integrin a11 was characterized in patient tumour tissue samples both at protein and mRNA level, and compared with a-SMA, one of a previously established CAF marker of poor prognosis in oral and tongue carcinoma. Our results showed that integrin a11 was overexpressed in the stroma of head and neck cancer compared with normal mucosa and correlated positively with the expression of a-SMA. The differences obtained by analysing the expression of a-SMA at the invasive tumour front (ITF) versus tumour centre (TC) pinpointed the importance of selection of relevant tumour region, when evaluating a potential biomarker. </p>
<p>Furthermore, the putative biological role of integrin a11 for the development of oral carcinoma was studied in integrin all knockout (KO) SCID mice versus wild type (WT) SCID mice, by exposing them to a chemical carcinogen (4NQO) in drinking water. An important role for a11 in the transition from a hyper proliferative stage till a malignant, invasive stage was indicated by the fact that the tumours formed in the KO mice took longer to develop from the oral papillomas and were smaller when compared to the tumours formed in the WT mice. </p>
<p>To study the role of a11 in human oral carcinogenesis, integrin a11 expression was also knocked-down in human oral CAFs by using shRNA constructs. CAFs with knocked-down integrin a11 showed lesser migration, were less efficient in remodelling the collagen matrix and supported a more shallow cancer cell invasion in 3D organotypic cultures when compared to control cells. </p>
<p>For in vivo studies, a microenviromentally-induced oral cancer mice model was developed. The use of a luciferase transfected oral dysplastic cell line assisted in the establishment of a non-invasive, yet consistent and more sensitive method of assessment of intraoral tumour progression. Co-injection of integrin a11 knocked-down CAFs the luciferase expressing dysplastic cell line induced smaller and less vascularized tumours than the control CAFs. </p>
<p>Taken together, the results of this work showed that expression of integrin a11 in oral cancer is increased at various levels in the stroma of oral cancer and plays a biological role for tumour progression both by directly affecting the invasive properties of oral cancer cells and by providing a pro-angiogenesis microenvironment. </p>
2016-04-29T00:00:00ZThe serum level of C-reactive protein (CRP) is associated with cognitive performance in acute phase psychosishttp://hdl.handle.net/1956/11957
The serum level of C-reactive protein (CRP) is associated with cognitive performance in acute phase psychosis
Johnsen, Erik; Fathian, Farivar; Kroken, Rune A; Steen, Vidar M; Jørgensen, Hugo A; Gjestad, Rolf; Løberg, Else-Marie
Journal article
Background Inflammatory processes have been implicated in the etiology of schizophrenia and related psychoses, in which cognitive deficits represent core symptoms. The aim of the present study was to investigate possible associations between the level of the inflammation marker C-reactive protein (CRP) and cognitive performance in patients through the acute phase of psychosis. Methods A total of 124 patients were assessed at admittance to hospital and 62 patients were retested at discharge or after 6 weeks at the latest, with measurements of the CRP levels and alternative forms of the Repeatable Battery for the Assessment of Neuropsychological Status. Results There was an inverse relationship between overall cognitive performance and CRP level at admittance. The association increased in sub-analyses including only patients with schizophrenia. In cognitive subdomain analyses statistically significant inverse associations were found between the CRP level and Delayed memory and Attention, respectively. No associations were found between CRP level and other measures of psychopathology including psychosis symptoms, depression, or functioning. At follow-up the association between CRP level and cognition was no longer present. There was a significant increase in cognitive performance between baseline and follow-up. There was a stronger increase in overall cognition scores in patients with higher baseline CRP levels. Conclusions The findings indicate that signs of inflammation may serve as a state-dependent marker of cognitive dysfunctions in acute psychosis. Trial registration ClinicalTrials.gov ID; NCT00932529 , registration date: 02.07.2009
2016-03-14T00:00:00ZGlobal epidemiology of gastrointestinal stromal tumours (GIST): A systematic review of population-based cohort studieshttp://hdl.handle.net/1956/11924
Global epidemiology of gastrointestinal stromal tumours (GIST): A systematic review of population-based cohort studies
Søreide, Kjetil; Sandvik, Oddvar Mathias; Søreide, Jon Arne; Giljaca, Vanja; Jureckova, Andrea; Bulusu, V. Ramesh
Journal article
<p>Background: Gastrointestinal stromal tumours (GISTs) are rare, yet the most common mesenchymal tumour within the digestive tract. Lack of diagnostic criteria and no specific code in the ICD system has prevented epidemiological evaluation except from overt malignant cases in the past. A global estimate of incidence and disease patterns has thus not been available.</p>
<p>Methods: A systematic literature search of all available population-based studies on GIST published between January 2000 and December 2014 were reviewed. Descriptive epidemiological data are presented.</p>
<p>Results: The search found 29 studies of more than 13,550 patients from 19 countries that reported sufficient data for regional or national population-based statistics. Age at diagnosis ranged from 10 to 100 years, with median age being mid 60s across most studies. Gender distribution was equal across studies. On average, 18% of patients had an incidental diagnosis (range from 5% to 40%). Anatomical location of primary tumour in 9747 GISTs demonstrated gastric location as the most frequent (55.6%) followed by small bowel (31.8%), colorectal (6.0%), other/various location (5.5%) and oesophagus (0.7%). Most studies reported incidence at 10&ndash;15 per million per year. Notably, lowest incidence was in China (Shanxi province) with 4.3 per million per year. Highest incidence rates were reported also from China (Hong Kong and Shanghai areas), and in Taiwan and Norway (Northern part), with up to 19&ndash;22 per million per year.</p>
<p>Conclusions: Epidemiology of GIST demonstrates some consistent features across geographical regions. Whether the reported extreme differences in incidence reflect real variation in population risk warrants further investigation.</p>
2015-02-01T00:00:00ZA 60-year follow-up of the incidence and prevalence of multiple sclerosis in Hordaland County, Western Norwayhttp://hdl.handle.net/1956/11909
A 60-year follow-up of the incidence and prevalence of multiple sclerosis in Hordaland County, Western Norway
Grytten, Nina; Aarseth, Jan Harald; Lunde, Hanne Marie; Myhr, Kjell-Morten
Journal article
<p>Objective: Investigate the incidence of multiple sclerosis during 1953&ndash;2013 and estimate the prevalence rate of MS on 1 January 2003 and 2013 in Hordaland County, Western Norway.</p>
<p>Methods: All patients with onset of disease in Hordaland 1953&ndash;2013 were identified in files from previous studies until 2003 and from patient records at the departments of Neurology, Haukeland University Hospital and Haugesund Hospital during 2003&ndash;2013. 1558 patients were assessed and 1402 of these were included, of whom 1035 were alive and living in Hordaland at prevalence day 1 January 2013. Annual incidence rates were calculated for 1953&ndash;2013.</p>
<p>Results: On 1 January 2003, the crude prevalence rate was 191/100 000 population and on 1 January 2013, the crude prevalence rate was 211.4 (95% CI 198.3 to 224.2) per 100 000; 270.9 (95% CI 250.6 to 292.3) for women and 151.8 (95% CI 136.8 to 167.9) for men. Prevalence peaked at ages 55&ndash;59 years for women and 60&ndash;64 years for men. The annual incidence rate increased from 1.9 (95% CI 1.2 to 2.6) per 100 000 during 1953&ndash;1957 to 7.2 (95% CI 6.0 to 8.5) during 1978&ndash;1982 and to 8.5 (95% CI 7.3 to 9.7) during 2003&ndash;2007, thus indicating a stabilising incidence over the past 35 years. The female/ male ratio ranged from 1.2:1 to 1.8:1 (p=0.381) during the period.</p>
<p>Conclusions: Stabilising rather than increasing incidence combined with the stable female/male ratio are indicative of non-fluctuating environmental factors in a geographical area otherwise characterised by lack of vitamin D effective sun exposure. The rising prevalence of MS could result from improved survival and follow-up methodology.</p>
2015-01-14T00:00:00ZPercutaneous cholecystostomy in acutecholecystitis; a retrospective analysis of a largeseries of 104 patientshttp://hdl.handle.net/1956/11902
Percutaneous cholecystostomy in acutecholecystitis; a retrospective analysis of a largeseries of 104 patients
Viste, Asgaut; Jensen, Dag Kjartan; Angelsen, Jon-Helge; Hoem, Dag
Journal article
<p>Background: The purpose of this study was to evaluate the clinical course and possible benefit of a percutaneous cholecystostomy in patients with acute cholecystitis.</p>
<p>Methods: Retrospective study of 104 patients with severe cholecystitis or cholecystitis not responding to antibiotic therapy treated with percutaneous drainage of the gall bladder (PC) during the period 2007 &ndash; 2013. Primary outcome was relief of cholecystitis, complications following the procedure and need for later cholecystectomy.</p>
<p>Results: There were 57 men and 47 women with a median age of 73,5 years (range 22 &ndash; 96). 43% of the patients were ASA III or IV and 91% had cholecystitis Grade 2 or 3. About 60% of the patients had severe comorbidity (cardiovascular disease or active cancer). Drain insertion was successful in all but one patient and complications were mild, apart from two patients that needed percutaneous drainage of intraabdominal fluid collection due to bile leakage. The drain was left in place for 1 &ndash; 75 days (median 6,5). When evaluated clinically and by blood tests (CRP and white blood cell counts) we found resolution of symptoms in 101 patients (97,2%), whereas 2 patients had no obvious effect of drainage. Four patients died within 30 days, no deaths were related to the drainage procedure. Follow-up after drainage was median 12 months (range 0 &ndash; 78). During that time cholecystectomy was performed in 30 patients and 24 patients had died. Following cholecystectomy, two had died, both from cancer
and more than one year after the operation.</p>
<p>Conclusion: Patients with acute cholecystitis were promptly relieved from their symptoms following PC. There were only minor complications following the procedure and only about 30% of the patients had a later
cholecystectomy.</p>
2015-03-08T00:00:00ZDisease-modifying treatments for multiple sclerosis – a review of approved medicationshttp://hdl.handle.net/1956/11895
Disease-modifying treatments for multiple sclerosis – a review of approved medications
Torkildsen, Øivind; Myhr, Kjell-Morten; Bø, Lars
Journal article
<p>Background and purpose: There is still no curative treatment for multiple sclerosis
(MS), but during the last 20 years eight different disease-modifying compounds
have been approved for relapsing remitting MS (RRMS).</p>
<p>Methods: A literature search was conducted on published randomized controlled
phase III trials indexed in PubMed on the approved medications until
21 May 2015.</p>
<p>Results: In this review the mode of action, documented treatment effects and
side effects of the approved MS therapies are briefly discussed.</p>
<p>Conclusions: Based on current knowledge of risk benefit of the approved MS
medications, including factors influencing adherence, it is suggested that oral
treatment with dimethyl fumarate or teriflunomide should be preferred as a
starting therapy amongst the first-line preparations for de novo RRMS. In the
case of breakthrough disease on first-line therapy, or rapidly evolving severe
RRMS, second-line therapy with natalizumab, fingolimod or alemtuzumab
should be chosen based on careful risk benefit stratification.</p>
2015-11-13T00:00:00ZSurgical treatment of shoulder instability in Norway. The Norwegian Shoulder Instability Registerhttp://hdl.handle.net/1956/11889
Surgical treatment of shoulder instability in Norway. The Norwegian Shoulder Instability Register
Blomquist, Jesper
Doctoral thesis
<p>Shoulder dislocation affects approximately 1300 person per year in Norway. The dislocation is normally caused by a fall on the outstretched arm. Many of the patients develop chronic recurrent instability, where the shoulder joint re-dislocates during sport activity or daily living. Other patients experience habitual chronic instability without an initial trauma. </p> <p>The current thesis has evaluated the surgical treatment of shoulder instability using data from the Norwegian Shoulder Instability Register that was established as a part of the project. The results are published in three papers. </p> <p>In Paper I we reported that the annual incidence rate of shoulder stabilisation surgery was 12 per 100.000 inhabitants. Compared to the annual incidence of shoulder dislocations approximately 40% of the patient with a primary dislocation underwent surgery. Anterior instability accounted for 83% of the procedures whereas posterior and multi-directional instability constituted 10% and 7% respectively. An arthroscopic labral repair (Bankart) was performed in 88% of the patients with primary anterior instability. In revision cases an open technique was used for 50% of the patients and coracoid transfer (Latarjet) was the dominating technique performed with an open approach. There was a significant improvement of the functional score for all patient groups. Primary anterior Bankart had a 1-year outcome of 75% on the WOSI score and a recurrence rate of 10%. Patients with posterior instability had a slightly worse WOSI score at follow-up (63%), and a recurrence rate of 16%.</p> <p>In Paper II we investigated if postoperative prescription of non-steroid anti- inflammatory drugs, NSAIDs, had any effect on the outcome after arthroscopic Bankart. In total only one third of the patients were treated with NSAIDs in the postoperative phase. The outcome for patients treated with and without NSAIDs did not differ after a mean follow up of 21 months. WOSI score was 75% and recurrence rate 12% for patient with NSAID treatment. For the control group the corresponding figures were 74 and 14%. Reoperation rates were 5% in both groups. 43% of the patients treated with an arthroscopic Bankart had an ambulatory procedure. 54% of the outpatients had non-steroid anti-inflammatory drugs, NSAIDs, prescribed post-operatively, compared to 19% of the inpatients. The result implies that postoperative use of NSAID in moderate dosages does not affect the outcome of arthroscopic Bankart and that it may facilitate ambulatory surgery. </p> <p>In paper III the outcomes of arthroscopic Bankart and open Latarjet were compared. After a mean 2.7 years follow-up we found a significantly higher recurrence rate of 17% after arthroscopic Bankart, compared to 7% after open Latarjet. There was a significant improvement but no difference between the treatment groups in the functional outcome, with a WOSI score of 74% for arthroscopic Bankart and 75% for Latarjet. Patients with recurrence of instability did not improve their score. Item analysis of the WOSI score indicated that patient with a Latarjet felt more secure on the stability of their shoulder, but had a lower score on mobility. </p> <p>In multiple logistic regression analysis the risk of recurrence after arthroscopic Bankart was further emphasised, with an odds ratio (OR) of 12.8 (CI 95%: 1.45-113, p=0.002). Age below 20 years at time of surgery was a risk factor for recurrence after both procedures (OR 2.24, CI 95%: 1.36-3.69, p=0.002). A combination of glenoid bone loss and an engaging Hill Sachs lesion was a risk factor for recurrence after arthroscopic Bankart (OR 12.6, CI 95%: 1.61-98, p=0.014), but not after a Latarjet procedure. </p> <p>WOSI for revision patients was 67% for arthroscopic Bankart and 65% for Latarjet at follow-up, with recurrence rates of 24 vs. 17%. WOSI-score was significantly lower for revisions compared to primary procedures (p<0.05), but there was no statistical significant difference between the two techniques. This thesis supports previous studies that have shown a high recurrence rate after arthroscopic Bankart. The Latarjet procedure had significantly fewer recurrence events, despite a higher proportion of patients with bone loss. Still, there was no difference in the functional outcome, indicating that there may be other drawbacks with this treatment. Patients with bone loss, especially when present on both the humerus and glenoid, seem to profit on treatment with a Latarjet procedure. Patient below 20 years of age has a poor prognosis for both treatment options.
2016-02-12T00:00:00ZShoulder instability surgery in Norway. The first report from a multicenter register, with 1-year follow-uphttp://hdl.handle.net/1956/11863
Shoulder instability surgery in Norway. The first report from a multicenter register, with 1-year follow-up
Blomquist, Jesper
Journal article
<p>Background and purpose. In January 2008, we established the Norwegian Register for Shoulder Instability Surgery. We report on the establishment, the baseline data, and the results at 1-year follow-up. </p> <p>Methods. Primary and revision shoulder stabilization is reported by the surgeon on a 1-page paper form containing the patient's history of shoulder injury, clinical findings, and perioperative findings. The WOSI questionnaire for self-assessment of shoulder function is completed at baseline and at follow-up after 1, 2, and 5 years. To evaluate the completeness of registration, we compared our data with those in the Norwegian Patient Registry (NPR). </p> <p>Results. The NPR reported 39 hospitals performing shoulder stabilizations. 20 of these started to report to our register during 2009, and 464 procedures (404 primary, 59 revisions) were included up to December 31, 2009, which represented 54% of the procedures reported to NPR. Of the 404 primary procedures, 83% were operations due to anterior instability, 10% were operations due to posterior instability, and 7% were operations due to multidirectional instability. Arthroscopic soft tissue techniques were used in 88% of the patients treated for primary anterior instability and open coracoid transfer was used in 10% of such patients. At 1-year follow-up of 213 patients, we found a statistically significantly improved WOSI score in all types of instability. 10% of the patients treated with arthroscopic anterior labral repair and 16% treated with arthroscopic posterior labral repair reported recurrent instability. No statistically significant difference in functional improvement or rate of recurrence was found between these groups. </p> <p>Interpretation. The functional results are in accordance with those in previous studies. However, the incidence of recurrent instability 1 year after arthroscopic labral repair is higher than expected. </p>
2011-11-23T00:00:00ZThe relation between celiac disease, nonceliac gluten sensitivity and irritable bowel syndromehttp://hdl.handle.net/1956/11855
The relation between celiac disease, nonceliac gluten sensitivity and irritable bowel syndrome
El-Salhy, Magdy; Hatlebakk, Jan Gunnar; Gilja, Odd Helge; Hausken, Trygve
Journal article
Wheat products make a substantial contribution to the dietary intake of many people worldwide. Despite the many beneficial aspects of consuming wheat products, it is also responsible for several diseases such as celiac disease (CD), wheat allergy, and nonceliac gluten sensitivity (NCGS). CD and irritable bowel syndrome (IBS) patients have similar gastrointestinal symptoms, which can result in CD patients being misdiagnosed as having IBS. Therefore, CD should be excluded in IBS patients. A considerable proportion of CD patients suffer from IBS symptoms despite adherence to a gluten-free diet (GFD). The inflammation caused by gluten intake may not completely subside in some CD patients. It is not clear that gluten triggers the symptoms in NCGS, but there is compelling evidence that carbohydrates (fructans and galactans) in wheat does. It is likely that NCGS patients are a group of self-diagnosed IBS patients who self-treat by adhering to a GFD.
2015-09-07T00:00:00ZThe patient perspective: Quality of life in advanced heart failure with frequent hospitalisationshttp://hdl.handle.net/1956/11851
The patient perspective: Quality of life in advanced heart failure with frequent hospitalisations
Nieminen, Markku S.; Dickstein, Kenneth; Fonseca, Cândida; Serrano, Jose Magaña; Parissis, John; Fedele, Francesco; Wikström, Gerhard; Agostoni, Piergiuseppe; Atar, Shaul; Baholli, Loant; Brito, Dulce; Colet, Josep Comin; Édes, István Ferenc; Gómez Mesa, Juan E.; Gorjup, Vojka; Garza, Eduardo Herrera; González Juanatey, José R.; Karanovic, Nenad; Karavidas, Apostolos; Katsytadze, Igor; Kivikko, Matti; Matskeplishvili, Simon; Merkely, Béla; Morandi, Fabrizio; Novoa, Angel; Oliva, Fabrizio; Ostadal, Petr; Pereira-Barretto, Antonio; Pollesello, Piero; Rudiger, Alain; Schwinger, Robert HG; Wieser, Manfred; Yavelov, Igor; Zymlinski, Robert
Journal article
End of life is an unfortunate but inevitable phase of the heart failure patients' journey. It is often preceded by a stage in the progression of heart failure defined as advanced heart failure, and characterised by poor quality of life and frequent hospitalisations. In clinical practice, the efficacy of treatments for advanced heart failure is often assessed by parameters such as clinical status, haemodynamics, neurohormonal status, and echo/MRI indices. From the patients' perspective, however, quality-of-life-related parameters, such as functional capacity, exercise performance, psychological status, and frequency of re-hospitalisations, are more significant. The effects of therapies and interventions on these parameters are, however, underrepresented in clinical trials targeted to assess advanced heart failure treatment efficacy, and data are overall scarce. This is possibly due to a non-universal definition of the quality-of-life-related endpoints, and to the difficult standardisation of the data collection. These uncertainties also lead to difficulties in handling trade-off decisions between quality of life and survival by patients, families and healthcare providers. A panel of 34 experts in the field of cardiology and intensive cardiac care from 21 countries around the world convened for reviewing the existing data on quality-of-life in patients with advanced heart failure, discussing and reaching a consensus on the validity and significance of quality-of-life assessment methods. Gaps in routine care and research, which should be addressed, were identified. Finally, published data on the effects of current i.v. vasoactive therapies such as inotropes, inodilators, and vasodilators on quality-of-life in advanced heart failure patients were analysed.
2015-07-15T00:00:00ZFunctional imaging to promote individualized and targeted therapy in endometrial cancerhttp://hdl.handle.net/1956/11834
Functional imaging to promote individualized and targeted therapy in endometrial cancer
Husby, Jenny Hild Aase
Doctoral thesis
<p>Background: Endometrial carcinoma is the most common pelvic malignancy in the Western world and the incidence is increasing. Endometrial carcinomas are surgically staged according to FIGO 2009 criteria, and the lack of robust preoperative staging methods results in overtreatment of this patient population, mostly by unnecessary invasive surgery and lymphadenectomy in patients with localized disease. New imaging methods are highly warranted to aid more accurate preoperative staging and thus potentially reduce unwanted post-operative side effects, decrease the amount of unnecessary resource-demanding surgery and to provide better individualized therapy for this patient group. </p> <p>Aims: Promote individualized treatment, reduce morbidity and facilitate implementation of targeted therapy among endometrial carcinoma patients by investigating functional and structural imaging biomarkers in pre-operatively acquired MRI and FDG-PET/CT. </p> <p>Methods: All patients with histologically confirmed endometrial carcinoma at Haukeland University Hospital were consecutively referred to pre-operative MRI and/or FDG-PET/CT for a period of four years. Images were individually read by two to four radiologists and nuclear medicine physicians conducting staging and image quantifications in a standard imaging report. Results were compared to the results of surgical staging regarding the tumors depth of myometrial invasion, cervical stromal involvement and the presence of lymph node metastases, these three criteria being well-established parameters predicting aggressiveness of disease and survival in endometrial cancer. </p> Main Results: The evaluation of the staging criteria depth of myometrial invasion, cervical stromal involvement and the presence of lymph node metastases on pre- operative 1.5T MRI are prone to considerable inter-observer variability (κ=0.4, 0.5 and 0.6, respectively), and the staging accuracy is variable with a sensitivity (specificity) of 80%, 63% and 38% respectively (53%, 94% and 100%, respectively). For image quantifications, the inter-observer agreement is good (ICC=0.56-0.98) and the measured parameters show significant correlations to established staging criteria. Tumor apparent diffusion coefficient (ADC) value on diffusion-weighted imaging (DWI) is significantly lower in tumors with deep myometrial invasion (ADC = 0.75 × 10-3mm2/s) compared with tumors with superficial or no myometrial invasion (ADC = 0.85 × 10-3mm2/s; p < 0.001), and the ADC value is negatively correlated to tumor size (p=0.007). Large tumor size measured on preoperative MRI is associated with reduced progression/recurrence free survival (p ≤ 0.005 for all size parameters), and CC diameter has an independent impact on survival (adjusted hazards ratio, 1.04; p = 0.009). FDG-PET/CT is excellent in ruling out lymph node metastases (NPV=97%) and SUVmax, SUVmean, MTV and TLG are significantly related to deep myometrial invasion, presence of lymph node metastases and high histological grade (p<0.015 for all). Calculated optimal cut-off values for MTV in predicting deep myometrial invasion (20 ml) and presence of lymph node metastases (30 ml), yield ORs of 7.8 (p<0.001) and 16.5 (p=0.001), respectively, outperforming the current pre-operative ground for decision-making based on pathology findings in endometrial biopsies. Conclusion: Functional and structural imaging biomarkers from MRI and FDG- PET/CT are promising for preoperative identification of high-risk patients in endometrial carcinoma.
2016-02-05T00:00:00ZMammographic density and histopathologic characteristics of screen-detected tumors in the Norwegian Breast Cancer Screening Programhttp://hdl.handle.net/1956/11832
Mammographic density and histopathologic characteristics of screen-detected tumors in the Norwegian Breast Cancer Screening Program
Moshina, Nataliia; Ursin, Giske; Hoff, Solveig Roth; Akslen, Lars A.; Roman, Marta; Sebuødegård, Sofie; Hofvind, Solveig
Journal article
<p>Background. High mammographic density might mask breast tumors, resulting in delayed diagnosis or missed cancers. </p>
<p>Purpose. To investigate the association between mammographic density and histopathologic tumor characteristics (histologic type, size, grade, and lymph node status) among women screened in the Norwegian Breast Cancer Screening Program. </p>
<p>Material and Methods. Information about 1760 screen-detected ductal carcinoma in situ (DCIS) and 7366 invasive breast cancers diagnosed among women aged 50–69 years, 1996–2010, was analyzed. The screening mammograms were classified subjectively according to the amount of fibroglandular tissue into fatty, medium dense, and dense by breast radiologists. Chi-square test was used to compare the distribution of tumor characteristics by mammographic density. Odds ratio (OR) of tumor characteristics by density was estimated by means of logistic regression, adjusting for screening mode (screen-film and full-field digital mammography), and age. </p>
<p>Results. Mean and median tumor size of invasive breast cancers was 13.8 and 12 mm, respectively, for women with fatty breasts, and 16.2 and 14 mm for those with dense breasts. Lymph node positive tumors were identified among 20.6% of women with fatty breasts compared with 27.2% of those with dense breasts (P < 0.001). The proportion of DCIS was significantly lower for women with fatty (15.8%) compared with dense breasts (22.0%). Women with dense breasts had an increased risk of large (OR, 1.44; 95% CI, 1.18–1.73) and lymph node positive tumors (OR, 1.26; 95% CI, 1.05–1.51) compared with women with fatty and medium dense breasts. Conclusion. High mammographic density was positively associated with tumor size and lymph node positive tumors.
2015-09-18T00:00:00ZParaneoplastic syndrome-associated neuronal antibodies in adult ADHDhttp://hdl.handle.net/1956/11831
Paraneoplastic syndrome-associated neuronal antibodies in adult ADHD
Haukanes, Bjørn Ivar; Hegvik, Tor-Arne; Eichler, Tilo Wolf; Haavik, Jan; Vedeler, Christian A.
Journal article
A high seroprevalence of Yo antibodies targeting cerebellar Purkinje cells was recently reported in children with attention deficit/hyperactivity disorder (ADHD). We investigated the presence of 8 paraneoplastic neurological syndrome (PNS)-associated antibodies including anti-Yo in 169 adult ADHD patients. No associations between ADHD and serum Yo antibodies or other antibodies associated with PNS were found. However, 10 out of 48 ADHD patient sera analyzed by immunofluorescence presented antibodies targeting cerebellar Purkinje cells. This reactivity probably represents the presence of low levels of antibodies against multiple cellular hitherto unknown antigens with little to no clinical significance.
2015-09-01T00:00:00ZCosts analysis and comparison of usefulness of acute MRI and 2 weeks of cast immobilization for clinically suspected scaphoid fractureshttp://hdl.handle.net/1956/11829
Costs analysis and comparison of usefulness of acute MRI and 2 weeks of cast immobilization for clinically suspected scaphoid fractures
Bergh, Torbjørn Hiis; Steen, Knut; Lindau, Tommy; Soldal, Lars Atle; BERNARDSHAW, SOOSAIPILLAI; Lunde, Lene; Lie, Stein Atle; Brudvik, Christina
Journal article
<p>Background and purpose &mdash; Fractures of the scaphoid are often not detected on initial plain radiographs. Conventional management of clinically suspected scaphoid fractures is cast immobilization for 2 weeks and then reassessment. Early MRI is a diagnostic alternative. We compared the cost and usefulness of the early MRI diagnostic strategy with that of conventional management.</p>
<p>Patients and methods &mdash; This prospective pseudo-randomized study included patients between 18 and 49 years of age who attended Bergen Accident and Emergency Department, Bergen, Norway during 1 year in 2009&ndash;2010, after sustaining an acute wrist trauma in the previous week and with a clinically suspected scaphoid fracture. 61 patients were investigated with acute MRI, while 63 patients received standard treatment as a control group. We used cost-minimization analysis to estimate the cost of the 2 patient groups.</p>
<p>Results &mdash; Concerning cost, there were no statistically significant differences in the total direct medical costs or in indirect costs between the groups. Concerning usefulness, patients in the MRI group without a fracture (n = 35) used a cast for fewer days (mean 1 day) than patients in the control group with no fractures (n = 52) (mean 14 days; p &lt; 0.001). They had less than half the number of days on sick leave than patients in the control group (mean 7 days vs. 15 days; p = 0.002).</p>
<p>Interpretation &mdash; In a Norwegian setting, an early MRI was of value in patients with clinically suspected scaphoid fracture and normal plain radiographs.</p>
2014-11-18T00:00:00ZCorrection: Reduction of late stillbirth with the introduction of fetal movement information and guidelines - a clinical quality improvementhttp://hdl.handle.net/1956/11822
Correction: Reduction of late stillbirth with the introduction of fetal movement information and guidelines - a clinical quality improvement
Tveit, Julie VH; Saastad, Eli; Stray-Pedersen, Babill; Børdahl, Per E; Flenady, Vicki; Fretts, Ruth; Frøen, J Frederik
Journal article
<p>We have performed a full cross-validation of this clinical Femina data collection against the routinely collected data of the Medical Birth Registry of Norway to validate the estimates of reduced mortality in the total population. The original estimate of fewer deaths during the intervention with OR 0.7 remains virtually unchanged for the original data collection. </p>
<p>The validation procedures revealed inaccuracies in data from the Medical Birth Registry of Norway for a partial comparison with mortality outside the study area, and we here correct this comparison. We present new, corrected and cross-validated data. Despite comparability issues, the most robust and cross-validated estimates confirm similar estimates of reduced mortality during the quality improvement intervention. </p>
<p>The online version of the original article can be found at <a href="http://dx.doi.org/ 10.1186/1471-2393-9-32" target="blank"> 10.1186/1471-2393-9-32</a> </p>
2010-09-02T00:00:00ZLong-range evolutionary constraints reveal cis-regulatory interactions on the human X chromosomehttp://hdl.handle.net/1956/11803
Long-range evolutionary constraints reveal cis-regulatory interactions on the human X chromosome
Naville, Magali; Ishibashi, Minaka; Ferg, Marco; Bengani, Hemant; Rinkwitz, Silke; Krecsmarik, Monika; Hawkins, Thomas A.; Wilson, Stephen W.; Manning, Elizabeth; Chilamakuri, Chandra Sekhar Reddy; Wilson, David I.; Louis, Alexandra; Raymond, F. Lucy; Rastegar, Sepand; Strähle, Uwe; Lenhard, Boris; Bally-Cuif, Laure; van Heyningen, Veronica; Fitzpatrick, David R.; Becker, Thomas S.; Crollius, Hugues Roest
Journal article
Enhancers can regulate the transcription of genes over long genomic distances. This is thought to lead to selection against genomic rearrangements within such regions that may disrupt this functional linkage. Here we test this concept experimentally using the human X chromosome. We describe a scoring method to identify evolutionary maintenance of linkage between conserved noncoding elements and neighbouring genes. Chromatin marks associated with enhancer function are strongly correlated with this linkage score. We test >1,000 putative enhancers by transgenesis assays in zebrafish to ascertain the identity of the target gene. The majority of active enhancers drive a transgenic expression in a pattern consistent with the known expression of a linked gene. These results show that evolutionary maintenance of linkage is a reliable predictor of an enhancer’s function, and provide new information to discover the genetic basis of diseases caused by the mis-regulation of gene expression.
2015-04-24T00:00:00ZFine mapping of genetic susceptibility loci for melanoma reveals a mixture of single variant and multiple variant regionshttp://hdl.handle.net/1956/11793
Fine mapping of genetic susceptibility loci for melanoma reveals a mixture of single variant and multiple variant regions
Barrett, Jennifer H.; Taylor, John C.; Bright, C; Harland, Mark; Dunning, Alison M; Akslen, Lars A.; Andresen, Per Arne; Avril, Marie-Francoise; Azizi, Esther; Scarra, Giovanna Bianchi; Brossard, Myriam; Brown, Kevin M.; Debniak, Tadeusz; Elder, David E.; Friedman, Eitan; Ghiorzo, Paola; Gillanders, Elizabeth M.; Gruis, Nelleke A.; Hansson, Johan; Helsing, Per; Hočevar, Marko; Höiom, Veronica; Ingvar, Christian; Landi, Maria Teresa; Lang, Julie L.; Lathrop, G. Mark; Lubinski, Jan; Mackie, Rona M.; Molven, Anders; Novakovic, Srdjan; Olsson, Håkan; Puig, Susana; Puig-Butille, Joan Anton; van der Stoep, Nienke; van Doorn, Remco; van Workum, Wilberg; Goldstein, Alisa M.; Kanetsky, Peter A.; Pharoah, Paul D.P.; Demenais, Florence; Hayward, Nicholas K.; Bishop, Julia A. Newton; Bishop, D. Timothy; Iles, Mark M.
Journal article
At least 17 genomic regions are established as harboring melanoma susceptibility variants, in most instances with genome-wide levels of significance and replication in independent samples. Based on genome-wide single nucleotide polymorphism (SNP) data augmented by imputation to the 1,000 Genomes reference panel, we have fine mapped these regions in over 5,000 individuals with melanoma (mainly from the GenoMEL consortium) and over 7,000 ethnically matched controls. A penalized regression approach was used to discover those SNP markers that most parsimoniously explain the observed association in each genomic region. For the majority of the regions, the signal is best explained by a single SNP, which sometimes, as in the tyrosinase region, is a known functional variant. However in five regions the explanation is more complex. At the CDKN2A locus, for example, there is strong evidence that not only multiple SNPs but also multiple genes are involved. Our results illustrate the variability in the biology underlying genome-wide susceptibility loci and make steps toward accounting for some of the “missing heritability.”
2015-08-14T00:00:00ZDiagnostic accuracy of a short endoscopic secretin test in patients with cystic fibrosishttp://hdl.handle.net/1956/11787
Diagnostic accuracy of a short endoscopic secretin test in patients with cystic fibrosis
Engjom, Trond; Erchinger, Friedemann Georg; Lærum, Birger Norderud; Tjora, Erling; Aksnes, Lage; Gilja, Odd Helge; Dimcevski, Georg Gjorgji
Journal article
<p>Objective: Short endoscopic secretin tests for exocrine pancreatic function are not properly evaluated in cystic fibrosis (CF).</p>
<p>Methods: Patients with CF and healthy controls (HCs) underwent endoscopic collection of duodenal juice between 30 and 45 minutes after secretin stimulation. Duodenal juice was analyzed for HCO3- concentration and pancreatic enzyme activities. Stool was analyzed for fecal elastase.</p>
<p>Results: Thirty-one patients with CF and 25 HCs were tested. Patients were classified as exocrine pancreatic sufficient (n = 13) or insufficient (n = 18). Both bicarbonate concentrations and enzyme activities in duodenal juice differentiated patients with CFI from patients with CFS and HC (P &lt; 0.001). The population displays strong correlation between severe CF genotype in both alleles and pancreatic insufficient phenotype (P &lt; 0.001). Conclusions: Pancreatic exocrine insufficient CF patients could be differentiated from exocrine sufficient patients and HCs using short endoscopic secretin test.</p>
2015-02-16T00:00:00ZAssociation of a BACE1 Gene Polymorphism with Parkinson’s Disease in a Norwegian Populationhttp://hdl.handle.net/1956/11781
Association of a BACE1 Gene Polymorphism with Parkinson’s Disease in a Norwegian Population
Lange, Johannes; Lunde, Kristin Aaser; Sletten, Camilla Johanne; Møller, Simon Geir; Tysnes, Ole-Bjørn; Alves, Guido; Larsen, Jan Petter; Maple-Grødem, Jodi
Journal article
Parkinson’s disease (PD) and Alzheimer’s disease (AD) share pathological features, including amyloid-beta pathology. Amyloid-beta peptide is generated by sequential proteolysis of amyloid precursor protein (APP), and genetic variations in the processing pathway genes have been found to increase the risk of AD; however, the contribution in PD is unknown. Methods. The aim of this study was to investigate whether candidate polymorphisms in five genes (ADAM10, BACE1, BACE2, PSEN2, and CLU) involved in the APP processing pathway affect PD risk in a population-based cohort of patients with incident PD and control subjects from the Norwegian ParkWest study. Results. We found an association of rs638405 in BACE1 with increased risk of PD, thus providing a novel link, at the genetic level, between amyloid-beta pathology and PD.
2015-01-01T00:00:00ZHydroxyapatite coating does not improve uncemented stem survival after total hip arthroplasty!: An analysis of 116,069 THAs in the Nordic Arthroplasty Register Association (NARA) databasehttp://hdl.handle.net/1956/11761
Hydroxyapatite coating does not improve uncemented stem survival after total hip arthroplasty!: An analysis of 116,069 THAs in the Nordic Arthroplasty Register Association (NARA) database
Hailer, Nils P.; Lazarinis, Stergios; Mäkelä, Keijo T.; Eskelinen, Antti; Fenstad, Anne Marie; Hallan, Geir; Havelin, Leif Ivar; Overgaard, Søren; Pedersen, Alma B.; Mehnert, Frank; Kärrholm, Johan
Journal article
<p>Background and purpose — It is still being debated whether HA coating of uncemented stems used in total hip arthroplasty (THA) improves implant survival. We therefore investigated different uncemented stem brands, with and without HA coating, regarding early and long-term survival.</p>
<p>Patients and methods — We identified 152,410 THA procedures using uncemented stems that were performed between 1995 and 2011 and registered in the Nordic Arthroplasty Register Association (NARA) database. We excluded 19,446 procedures that used stem brands less than 500 times in each country, procedures performed due to diagnoses other than osteoarthritis or pediatric hip disease, and procedures with missing information on the type of coating. 22 stem brands remained (which were used in 116,069 procedures) for analysis of revision of any component. 79,192 procedures from Denmark, Norway, and Sweden were analyzed for the endpoint stem revision. Unadjusted survival rates were calculated according to Kaplan-Meier, and Cox proportional hazards models were fitted in order to calculate hazard ratios (HRs) for the risk of revision with 95% confidence intervals (CIs). </p>
<p>Results — Unadjusted 10-year survival with the endpoint revision of any component for any reason was 92.1% (CI: 91.8–92.4). Unadjusted 10-year survival with the endpoint stem revision due to aseptic loosening varied between the stem brands investigated and ranged from 96.7% (CI: 94.4–99.0) to 99.9% (CI: 99.6–100). Of the stem brands with the best survival, stems with and without HA coating were found. The presence of HA coating was not associated with statistically significant effects on the adjusted risk of stem revision due to aseptic loosening, with an HR of 0.8 (CI: 0.5–1.3; p = 0.4). The adjusted risk of revision due to infection was similar in the groups of THAs using HA-coated and non-HA-coated stems, with an HR of 0.9 (CI: 0.8–1.1; p = 0.6) for the presence of HA coating. The commonly used Bimetric stem (n = 25,329) was available both with and without HA coating, and the adjusted risk of stem revision due to aseptic loosening was similar for the 2 variants, with an HR of 0.9 (CI: 0.5–1.4; p = 0.5) for the HA-coated Bimetric stem. </p>
<p>Interpretation — Uncemented HA-coated stems had similar results to those of uncemented stems with porous coating or rough sand-blasted stems. The use of HA coating on stems available both with and without this surface treatment had no clinically relevant effect on their outcome, and we thus question whether HA coating adds any value to well-functioning stem designs. </p>
2014-09-01T00:00:00ZEpidemiology and classification of gastroenteropancreatic neuroendocrine neoplasms using current coding criteriahttp://hdl.handle.net/1956/11741
Epidemiology and classification of gastroenteropancreatic neuroendocrine neoplasms using current coding criteria
Sandvik, Oddvar Mathias; Søreide, Kjetil; Gudlaugsson, Einar; Kvaløy, Jan Terje; Søreide, Jon Arne
Journal article
<p>Background: The lack of uniform criteria for coding of gastroenteropancreatic neuroendocrine neoplasia (GEP-NEN) has hampered previous epidemiological studies. The epidemiology of GEP-NEN was investigated in this study using currently available criteria.</p>
<p>Methods: All patients diagnosed with GEP-NEN between January 2003 and December 2013 in a well defined Norwegian population of approximately 350 000 people were included. Age- and sex-adjusted incidence rates were calculated. The current 2010 World Health Organization criteria, European Neuroendocrine Tumour Society classification and International Union Against Cancer (UICC) classification were used.</p>
<p>Results: A total of 204 patients (114 male, 55&middot;9 per cent) were identified. The median age at diagnosis was 61 (range 10&ndash;94) years. The annual overall crude incidence was 5&middot;83 per 100 000 inhabitants, with an increasing trend (P = 0&middot;033). The most frequent location was small intestine (60 patients, 29&middot;4 per cent) followed by appendix (48 patients, 23&middot;5 per cent) and pancreas (33 patients, 16&middot;2 per cent). Grade 1 tumours were more common in gastrointestinal (100 patients, 58&middot;5 per cent) than in pancreatic (9 patients, 27 per cent) NEN. According to the UICC classification, 77 patients (37&middot;7 per cent) had stage I, 17 patients (8&middot;3 per cent) stage II, 37 patients (18&middot;1 per cent) stage III and 70 patients (34&middot;3 per cent) had stage IV disease. No patient with stage I disease had grade 3 tumours; advanced tumour grade increased with stage.</p>
<p>Conclusion: A high crude incidence of GEP-NEN, at 5&middot;83 per 100 000 inhabitants, was noted together with a significant increasing trend over time.</p>
2016-02-01T00:00:00ZBioavailability of iron, zinc, folate and vitamin A when fortified in condiments and seasoningshttp://hdl.handle.net/1956/11733
Bioavailability of iron, zinc, folate and vitamin A when fortified in condiments and seasonings
Degerud, Eirik Magnus Meek; Manger, Mari Skar; Strand, Tor A.; Dierkes, Jutta
Journal article
Seasonings and condiments can be candidate vehicles for micronutrient fortification if consumed consistently and if dietary practices ensure bioavailability of the nutrient. In this review, we identify factors that may affect the bioavailability of iron, vitamin A, zinc, and folic acid when added to seasonings and condiments and evaluate their effects on micronutrient status. We take into consideration the chemical and physical properties of different forms of the micronutrients, the influence of the physical and chemical properties of foods and meals to which fortified seasonings and condiments are typically added, and interactions between micronutrients and the physiological and nutritional status of the target population. Bioavailable fortificants of iron have been developed for use in dry or fluid vehicles. For example, sodium iron ethylenediaminetetraacetic acid (NaFeEDTA) and ferrous sulfate with citric acid are options for iron fortification of fish and soy sauce. Furthermore, NaFeEDTA, microencapsulated ferrous fumarate, and micronized elemental iron are potential fortificants in curry powder and salt. Dry forms of retinyl acetate or palmitate are bioavailable fortificants of vitamin A in dry candidate vehicles, but there are no published studies of these fortificants in fluid vehicles. Studies of zinc and folic acid bioavailability in seasonings and condiments are also lacking.
2015-11-01T00:00:00ZThey know! - do they? A qualitative study of residents and relatives views on advance care planning, end-of-life care, and decision-making in nursing homes.http://hdl.handle.net/1956/11728
They know! - do they? A qualitative study of residents and relatives views on advance care planning, end-of-life care, and decision-making in nursing homes.
Bollig, Georg; Gjengedal, Eva; Rosland, Jan Henrik
Journal article
<p>Background: Residents living in long-term care facilities are a vulnerable population. For many residents, a nursing home is their place of death. Palliative care and end-of-life decisions are important components of their care provision.</p>
<p>Aim: To study the views of cognitively able residents and relatives on advance care planning, end-of-life care, and decision-making in nursing homes.</p>
<p>Design: A qualitative study with in-depth interviews with nursing home residents and focus group interviews with relatives of nursing home residents. Analysis is based on interpretive description.</p>
<p>Setting/participants: In total, 43 informants from nine nursing homes participated in the study (25 nursing home residents and 18 relatives). All included residents had capacity to provide informed consent and lived in long-term care.</p>
<p>Results: The main findings of this study were the differing views about decision-making and advance care planning of residents and relatives. Residents do trust relatives and staff to make important decisions for them. The relatives are in contrast insecure about the residents&rsquo; wishes and experience decision-making as a burden. The majority of the residents had not participated in advance care planning. None of the residents stated challenges connected to end-of-life care or mentioned the wish for euthanasia.</p>
<p>Conclusion: Although most residents seem to be satisfied with decision-making and end-of life care, there is a need for systematic advance care planning. Advance care planning could help to explore future wishes for care and ease decision-making for the relatives, physicians, and staff and should be offered to all cognitively able nursing homes residents.</p>
2015-01-01T00:00:00ZS100A16 promotes differentiation and contributes to a less aggressive tumor phenotype in oral squamous cell carcinomahttp://hdl.handle.net/1956/11727
S100A16 promotes differentiation and contributes to a less aggressive tumor phenotype in oral squamous cell carcinoma
Sapkota, Dipak; Bruland, Ove; Parajuli, Himalaya; Osman, Tarig Al-Hadi; Teh, Muy-Teck; Johannessen, Anne Christine; Costea, Daniela Elena
Journal article
<p>Background: Altered expression of S100A16 has been reported in human cancers, but its biological role in tumorigenesis is not fully understood. This study aimed to investigate the clinical significance and functional role of S100A16 in oral squamous cell carcinoma (OSCC) suppression.</p>
<p>Methods: S100A16 mRNA and/or protein levels were examined by quantitative RT-PCR and immunohistochemistry in whole- and laser microdissected-specimens of normal human oral mucosa (NHOM, n&thinsp;=&thinsp;65), oral dysplastic lesions (ODL, n&thinsp;=&thinsp;21), OSCCs (n&thinsp;=&thinsp;132) and positive cervical nodes (n&thinsp;=&thinsp;17). S100A16 protein expression in OSCC was examined for correlations with clinicopathological variables and patient survival. S100A16 was over-expressed and knocked-down in OSCC-derived (CaLH3 and H357) cells by employing retroviral constructs to investigate its effects on cell proliferation, sphere formation and three dimensional (3D)-organotypic invasive abilities in vitro and tumorigenesis in a mouse xenograft model.</p>
<p>Results: Both S100A16 mRNA and protein levels were found to be progressively down-regulated from NHOM to ODL and OSCC. Low S100A16 protein levels in OSCC significantly correlated with reduced 10-year overall survival and poor tumor differentiation. Analysis of two external OSCC microarray datasets showed a positive correlation between the mRNA expression levels of S100A16 and keratinocyte differentiation markers. CaLH3 and H357 cell fractions enriched for differentiated cells either by lack of adherence to collagen IV or FACS sorting for low p75NTR expression expressed significantly higher S100A16 mRNA levels than the subpopulations enriched for less differentiated cells. Corroborating these findings, retroviral mediated S100A16 over-expression and knock-down in CaLH3 and H357 cells led to respective up- and down-regulation of differentiation markers. In vitro functional studies showed significant reduction in cell proliferation, sphere formation and 3D-invasive abilities of CaLH3 and H357 cells upon S100A16 over-expression. These functional effects were associated with concomitant down-regulation of self-renewal (Bmi-1 and Oct 4A) and invasion related (MMP1 and MMP9) molecules. S100A16 over-expression also suppressed tumorigenesis of H357 cells in a mouse xenograft model and the resulting tumor xenografts displayed features/expression of increased differentiation and reduced proliferation/self-renewal.</p>
<p>Conclusions: These results indicate that S100A16 is a differentiation promoting protein and might function as a tumor suppressor in OSCC.</p>
2015-09-09T00:00:00ZEmergency resuscitative thoracotomy performed in European civilian trauma patients with blunt or penetrating injuries: a systematic reviewhttp://hdl.handle.net/1956/11722
Emergency resuscitative thoracotomy performed in European civilian trauma patients with blunt or penetrating injuries: a systematic review
Narvestad, Jon; Meskinfamfard, M.; Søreide, Kjetil
Journal article
<p>Purpose: Emergency resuscitative thoracotomy (ERT) is a lifesaving procedure in selected patients. Indications are still being debated, but outcome in blunt trauma is believed to be poor. Recent reports from European populations, where blunt trauma predominates, have suggested favorable outcome also in blunt trauma. Our aim was to identify all European studies reported over the last decade and compare reported outcomes to existing knowledge.</p>
<p>Methods: We performed a systematic literature search according to PRISMA guidelines (January 1st, 2004 to December 31st, 2014). The &ldquo;grey literature&rdquo; was included by searching Google Scholar. Qualitative comparison of studies and outcomes was done.</p>
<p>Results: A total of 8 articles from Europe were included originating from Croatia, Norway (n = 2), Denmark, Iceland, the Netherlands, Scotland, and Switzerland. Of 376 resuscitative thoracotomies, 193 (51.3 %) were for blunt trauma. Male:female distribution was 3.5:1. The collectively reported overall survival was 42.8 % (n = 161), with 25.4 % (49 of 193) blunt trauma and 61.2 % (112 of 183) penetrating injuries. When strictly including those ERTs designated as done in the emergency department for blunt mechanism (n = 139) only, a total of 18 patients survived (12.9 %). Survival after EDTs for penetrating trauma was 41.6 % (37 of 89). Neurological outcome (reported in 5 of 8 studies) reported favorable neurological long-term outcome in the majority of survivors, even after blunt trauma. None referred to Glasgow Outcome Score. Heterogeneity in the studies prevented outcome analyses by formal quantitative meta-analysis.</p>
<p>Conclusion: The reported outcome after ERT in European civilian trauma populations is favorable, with one in every four ERTs in the ED surviving. Notably, outcome is at variance with previously reported collective data, in particular for blunt trauma. Multicenter, prospective, observational data are needed to validate the modern role of ERT in blunt trauma.</p>
2015-01-01T00:00:00ZEstablishment of a bioluminescence model for microenvironmentally induced oral carcinogenesis with implications for screening bioengineered scaffolds.http://hdl.handle.net/1956/11721
Establishment of a bioluminescence model for microenvironmentally induced oral carcinogenesis with implications for screening bioengineered scaffolds.
Suliman, Salwa; Parajuli, Himalaya; Sun, Yang; Johannessen, Anne Christine; Finne-Wistrand, Anna; McCormack, Emmet; Mustafa, Kamal Babikeir Eln; Costea, Daniela Elena
Journal article
<p>Background: Microenvironmental cues play a major role in head and neck cancer. Biodegradable scaffolds used for bone regeneration might also act as stimulative cues for head and neck cancer. The purpose of this study was to establish an experimental model for precise and noninvasive evaluation of tumorigenic potential of microenvironmental cues in head and neck cancer.</p>
<p>Methods: Bioluminescence was chosen to image tumor formation. Early neoplastic oral keratinocyte (DOK) cells were luciferase-transduced (DOKLuc), then tested in nonobese diabetic severe combined immunodeficient IL2r&gamma;null mice either orthotopically (tongue) or subcutaneously for their potential as &ldquo;screening sensors&rdquo; for diverse microenvironmental cues.</p>
<p>Results: Tumors formed after inoculation of DOKLuc were monitored easier by bioluminescence, and bioluminescence was more sensitive in detecting differences between various microenvironmental cues when compared to manual measurements. Development of tumors from DOKLuc grown on scaffolds was also successfully monitored noninvasively by bioluminescence.</p>
<p>Conclusion: The model presented here is a noninvasive and sensitive model for monitoring the impact of various microenvironmental cues on head and neck cancer in vivo.</p>
2015-01-01T00:00:00ZCan the cardiovascular family history reported by our patients be trusted? The Norwegian Stroke in the Young Studyhttp://hdl.handle.net/1956/11720
Can the cardiovascular family history reported by our patients be trusted? The Norwegian Stroke in the Young Study
Øygarden, Halvor; Fromm, Annette; Sand, Kristin Modalsli; Eide, Geir Egil; Thomassen, Lars; Næss, Halvor; Waje-Andreassen, Ulrike
Journal article
<p>Background and purpose: Family history (FH) is used as a marker for inherited risk. Using FH for this purpose requires the FH to reflect true disease in the family. The aim was to analyse the concordance between young and middle-aged ischaemic stroke patients&#39; reported FH of cardiovascular disease (CVD) with their parents&#39; own reports.</p>
<p>Methods: Ischaemic stroke patients aged 15&ndash;60 years and their eligible parents were interviewed using a standardized questionnaire. Information of own CVD and FH of CVD was registered. Concordance between patients and parents was tested by kappa statistics, sensitivity, specificity, predictive values and likelihood ratios. Regression analyses were performed to identify patient characteristics associated with non-concordance of replies.</p>
<p>Results: There was no difference in response rate between fathers and mothers (P = 0.355). Both parents responded in 57 cases. Concordance between patient and parent reports was good, with kappa values ranging from 0.57 to 0.7. The patient-reported FH yielded positive predictive values of 75% or above and negative predictive values of 90% or higher. The positive likelihood ratios (LR+) were 10 or higher and negative likelihood ratios (LR&minus;) were generally 0.5 or lower. Interpretation regarding peripheral arterial disease was limited due to low parental prevalence. Higher age was associated with impaired concordance between patient and parent reports (odds ratio 1.05; 95% confidence interval 1.01&ndash;1.09; P = 0.020).</p>
<p>Conclusions: The FH provided by young and middle-aged stroke patients is in good concordance with parental reports. FH is an adequate proxy to assess inherited risk of CVD in young stroke patients.</p>
2016-01-01T00:00:00ZAirway management by physician-staffed Helicopter Emergency Medical Services – a prospective, multicentre, observational study of 2,327 patientshttp://hdl.handle.net/1956/11719
Airway management by physician-staffed Helicopter Emergency Medical Services – a prospective, multicentre, observational study of 2,327 patients
Sunde, Geir Arne; Heltne, Jon-Kenneth; Lockey, David; Burns, Brian; Sandberg, Mårten; Fredriksen, Knut; Hufthammer, Karl Ove; Soti, Akos; Lyon, Richard; Jäntti, Helena; Kämäräinen, Antti; Reid, Bjørn Ole; Silfvast, Tom; Harm, Falko; Sollid, Stephen J. M.
Journal article
<p>Background. Despite numerous studies on prehospital airway management, results are difficult to compare due to inconsistent or heterogeneous data. The objective of this study was to assess advanced airway management from international physician-staffed helicopter emergency medical services.</p>
<p>Methods. We collected airway data from 21 helicopter emergency medical services in Australia, England, Finland, Hungary, Norway and Switzerland over a 12-month period. A uniform Utstein-style airway template was used for collecting data. </p>
<p>Results. The participating services attended 14,703 patients on primary missions during the study period, and 2,327 (16 %) required advanced prehospital airway interventions. Of these, tracheal intubation was attempted in 92 % of the cases. The rest were managed with supraglottic airway devices (5 %), bag-valve-mask ventilation (2 %) or continuous positive airway pressure (0.2 %). Intubation failure rates were 14.5 % (first-attempt) and 1.2 % (overall). Cardiac arrest patients showed significantly higher first-attempt intubation failure rates (odds ratio: 2.0; 95 % CI: 1.5-2.6; p < 0.001) compared to non-cardiac arrest patients. Complications were recorded in 13 %, with recognised oesophageal intubation being the most frequent (25 % of all patients with complications). For non-cardiac arrest patients, important risk predictors for first-attempt failure were patient age (a non-linear association) and administration of sedatives (reduced failure risk). The patient’s sex, provider’s intubation experience, trauma type (patient category), indication for airway intervention and use of neuromuscular blocking agents were not risk factors for first-attempt intubation failure. </p>
<p>Conclusions. Advanced airway management in physician-staffed prehospital services was performed frequently, with high intubation success rates and low complication rates overall. However, cardiac arrest patients showed significantly higher first-attempt failure rates compared to non-cardiac arrest patients. All failed intubations were handled successfully with a rescue device or surgical airway. </p>
2015-08-07T00:00:00ZA pragmatic approach to sonothrombolysis in acute ischaemic stroke: The Norwegian randomised controlled sonothrombolysis in acute stroke study (NOR-SASS)http://hdl.handle.net/1956/11716
A pragmatic approach to sonothrombolysis in acute ischaemic stroke: The Norwegian randomised controlled sonothrombolysis in acute stroke study (NOR-SASS)
Nacu, Aliona; Kvistad, Christopher Elnan; Logallo, Nicola; Næss, Halvor; Waje-Andreassen, Ulrike; Aamodt, Anne Hege; Solhoff, Ragnar; Lund, Christian; Tobro, Håkon; Rønning, Ole Morten; Salvesen, Rolf; Idicula, Titto; Thomassen, Lars
Journal article
<p>Background: Ultrasound accelerates thrombolysis with tPA (sonothrombolysis). Ultrasound in the absence of tPA also accelerates clot break-up (sonolysis). Adding intravenous gaseous microbubbles may potentiate the effect of ultrasound in both sonothrombolysis and sonolysis. The Norwegian Sonothrombolysis in Acute Stroke Study aims in a pragmatic approach to assess the effect and safety of contrast enhanced ultrasound treatment in unselected acute ischaemic stroke patients.</p>
<p>Methods/Design: Acute ischaemic stroke patients &ge;18 years, with or without visible arterial occlusion on computed tomography angiography (CTA) and treatable&thinsp;&le;&thinsp;4&frac12;&thinsp;hours after symptom onset, are included in NOR-SASS. NOR-SASS is superimposed on a separate trial randomising patients with acute ischemic stroke to either tenecteplase or alteplase (The Norwegian Tenecteplase Stroke Trial NOR-TEST). The NOR-SASS trial has two arms: 1) the thrombolysis-arms (NOR-SASS A and B) includes patients given intravenous thrombolysis (tenecteplase or alteplase), and 2) the no-thrombolysis-arm (NOR-SASS C) includes patients with contraindications to thrombolysis. First step randomisation of NOR-SASS A is embedded in NOR-TEST as a 1:1 randomisation to either tenecteplase or alteplase. Second step NOR-SASS randomisation is 1:1 to either contrast enhanced sonothrombolysis (CEST) or sham CEST. Randomisation in NOR-SASS B (routine alteplase group) is 1:1 to either CEST or sham CEST. Randomisation of NOR-SASS C is 1:1 to either contrast enhanced sonolysis (CES) or sham CES. Ultrasound is given for one hour using a 2-MHz pulsed-wave diagnostic ultrasound probe. Microbubble contrast (SonoVue&reg;) is given as a continuous infusion for ~30 min. Recanalisation is assessed at 60 min after start of CEST/CES. Magnetic resonance imaging and angiography is performed after 24 h of stroke onset. Primary study endpoints are 1) major neurological improvement measured with NIHSS score at 24 h and 2) favourable functional outcome defined as mRS 0&ndash;1 at 90 days.</p>
<p>Discussion: NOR-SASS is the first randomised controlled trial designed to test the superiority of contrast enhanced ultrasound treatment given &le;4&frac12;&thinsp;hours after stroke onset in an unselected acute ischaemic stroke population eligible or not eligible for intravenous thrombolysis, with or without a defined arterial occlusion on CTA. If a positive effect and safety can be proven, contrast enhanced ultrasound treatment will be an option for all acute ischaemic stroke patients. EudraCT No 201200032341; www.​clinicaltrials.​gov NCT01949961.</p>
2015-07-11T00:00:00ZEpidemiology, comorbidity and clinical course of myasthenia gravis. A registry-based studyhttp://hdl.handle.net/1956/11708
Epidemiology, comorbidity and clinical course of myasthenia gravis. A registry-based study
Andersen, Jintana Bunpan
Doctoral thesis
<p>Background: Autoimmune myasthenia gravis (MG) is a rare neuromuscular transmission
disorder. The pathophysiologic mechanisms are well-studied, but the etiology remains unknown. The clinical course of MG is still characterized by remissions and exacerbations. Identifying prognostic factors may be helpful when choosing treatment strategies in MG patients. Studies on MG epidemiology report increasing prevalence and incidence of the disease. However, the reported data on MG epidemiology and of prognostic factors vary considerably, reflecting differences in study design, case ascertainment and measurements of clinical severity and outcome.</p>
<p>Objectives: First, we aimed to determine the prevalence, incidence and gender specific characteristics of MG patients needing drug treatment in a well-defined population cohort. Second, we examined the total drug treatment and comorbidity in MG patients. Finally, we aimed to assess the clinical course of MG, and to identify prognostic factors that may contribute to a good outcome in MG patients. </p>
<p>Materials & Methods: Patient information in papers I and II was retrieved from the Norwegian Prescription Database, which contains information on all prescription drugs expedited in Norway since 2004. In paper III, comprehensive clinical information on MG patients treated in a consistent fashion for over three decades was obtained from the Myasthenia Gravis Patient Database at Duke University Medical Center (North Carolina, USA). </p>
<p>Results & Conclusions: The point prevalence of symptomatic MG in a complete Norwegian cohort 1 January, 2008 was 131 per million inhabitants, and the incidence rate for the year 2007 was16 per million. Our calculated prevalence and incidence is in agreement with other population-based studies. MG patients are more often treated with non-MG prescription drugs than patients using drugs for most other conditions, reflecting frequent comedication and medical comorbidity. The prognosis of MG is favorable for the majority of patients, regardless of age, maximum disease severity and antibody status. </p>
2016-01-22T00:00:00ZStroke patients’ knowledge about cardiovascular family history – the Norwegian Stroke in the Young Study (NOR-SYS).http://hdl.handle.net/1956/11698
Stroke patients’ knowledge about cardiovascular family history – the Norwegian Stroke in the Young Study (NOR-SYS).
Øygarden, Halvor; Fromm, Annette; Sand, Kristin Modalsli; Eide, Geir Egil; Thomassen, Lars; Næss, Halvor; Waje-Andreassen, Ulrike
Journal article
<p>Background: Family history (FH) is a risk factor for cardiovascular disease, especially coronary artery disease (CAD). The impact on risk of stroke is less clear. This study investigated young and middle-aged ischemic stroke patients&rsquo; knowledge on FH of stroke, CAD, and peripheral artery disease (PAD) with a special regard to sex differences.</p>
<p>Methods: From September 2010 to February 2014, all ischemic stroke patients aged 15&ndash;60 years were prospectively included in the Norwegian Stroke in the Young Study (NOR-SYS). FH of stroke, CAD and PAD in offspring, siblings, parents, and grandparents was assessed using a standardized face-to-face interview. In addition to &lsquo;yes&rsquo; and &lsquo;no&rsquo;, the optional reply &lsquo;don&rsquo;t know&rsquo; was included to improve accuracy. McNemar&rsquo;s test was used to compare paired proportions, i.e. FH in male vs. female relatives. Multiple logistic regression analyses were used to test the influence of patient sex on FH reporting and to adjust for possible confounding factors.</p>
<p>Results: Altogether 257 patients were included. Mean age was 49.5 years and 68.1% were males. FH of cardiovascular disease was reported by 59% of patients. When asked about FH of stroke, 48 (18.7%) and 46 (17.9%) patients reported yes, whereas 17 (6.6%) and 9 (3.5%) reported &lsquo;don&rsquo;t know&rsquo; regarding father and mother respectively, similarly patients reported &lsquo;don&rsquo;t know&rsquo; regarding 117 (45.5%) paternal vs. 83 (32.4%) maternal grandmothers (p&thinsp;&lt;&thinsp;0.001). Female patients reported less &lsquo;don&rsquo;t know&rsquo; and were more likely to report a positive cardiovascular FH than males (OR: 3.4; 95% CI: 1.5 to 7.7; p&thinsp;=&thinsp;0.004). Patients had more detailed knowledge about CAD than stroke in fathers (p&thinsp;&lt;&thinsp;0.001), mothers (p&thinsp;&lt;&thinsp;0.001) and siblings (p&thinsp;=&thinsp;0.01).</p>
<p>Conclusions: Young and middle-aged stroke patients reported a high FH burden of cardiovascular disease. Females are more likely to report a positive FH than males. Detailed knowledge on FH was best for CAD. Our results suggest sex has a big impact on FH knowledge. Females have more knowledge of FH than males and knowledge is better for relatives with a female than male linkage.</p>
2015-03-12T00:00:00ZEstradiol measurement in translational studies of breast cancerhttp://hdl.handle.net/1956/11693
Estradiol measurement in translational studies of breast cancer
Lønning, Per Eystein
Journal article
Plasma estrogen measurement with use of radioimmunoassays has been instrumental in the development of aromatase inhibitors for endocrine therapy of postmenopausal breast cancer. However, due to low plasma estrogen concentrations in postmenopausal women, direct radioimmunoassays lack the sensitivity required. While certain laboratories have developed highly sensitive assays for research purposes revealing plasma estrogen suppression consistent with results from tracer studies, such assays are time and labor-consuming due to need for pre-analytical chromatographic purification, sample concentration and sometimes conversion of precursors to products. While novel chromatographic methods involving mass spectrometry analysis are likely to replace such radioimmunoassays in the future, so far a limited number of laboratories have developed suitable assays with a detection limit (around 1 pM) that is required for analyzing plasma estrogen levels in patients during treatment with potent aromatase inhibitors.
2015-07-01T00:00:00ZAssociation between Dietary Betaine Intake and Circulating Levels of Parameters Related to Choline Oxidation and Lipid Metabolism in Patients with Stable Angina Pectorishttp://hdl.handle.net/1956/11677
Association between Dietary Betaine Intake and Circulating Levels of Parameters Related to Choline Oxidation and Lipid Metabolism in Patients with Stable Angina Pectoris
Arnesen, Håkon
Master thesis
Cardiovascular disease (CVD) is among the leading causes of death worldwide, and is strongly influenced by lifestyle. Thus, promoting a healthy lifestyle, which includes having a healthy diet, is among the primary preventive strategies for reducing future risk of cardiovascular events. Elevated circulating total homocysteine (tHcy) is an independent risk factor for CVD. However, Hcy lowering treatment has not proven to reduce mortality or cardiovascular events among patients with CVD, and the mechanism linking tHcy to disease risk has not yet been discovered. Thus, the metabolic pathways surrounding Hcy, including the one-carbon metabolism and the choline oxidation pathway, are very interesting targets for investigation. Betaine is a micronutrient that is achieved mainly from the diet or endogenously by irreversible mitochondrial oxidation of choline. Betaine lowers tHcy concentrations in the liver and kidney by serving as a methyl donor in a reaction catalyzed by betaine- homocysteine methyltransferase. This reaction represents the first step along a transmethylation pathway, which provides three available methyl groups in the one-carbon metabolism. Betaine is thus considered to be an important modulator of the one-carbon metabolism. Furthermore, betaine-dependent remethylation of Hcy produces methionine. Betaine has thus been hypothesized to affect the hepatic lipid metabolism by producing sufficient amounts of methionine which enters a pathway that ultimately leads to increased synthesis and secretion of lipid-rich very-low density lipoproteins (VLDLs). Objective: The main aim of the current study was to explore the associations of reported dietary betaine intake with circulating levels of metabolites along to the choline oxidation pathway and lipid related parameters in patients diagnosed with stable angina pectoris (SAP). A secondary aim was to explore potential effect modification by folate status and statin treatment. Methods: This cross-sectional study was based on the Western Norway B-vitamin Intervention Trial, and included 2026 SAP patients with angiographically verified coronary artery disease, and available dietary data. Average daily dietary intakes during the recent year were assessed by a 169-item food frequency questionnaire. Standard blood laboratory parameters were measured according to routine protocols at the two university hospitals in Western Norway. The associations between reported dietary betaine intake and one-carbon metabolites, including choline oxidation, were assessed by Spearman´s rank correlations, adjusted for age, gender, total energy intake and statin treatment. Multiple linear regression was used to explore the relationship between reported dietary betaine intake by quartiles and according to the upper decile, and levels of lipid related parameters, and were adjusted for age, gender, body mass index (BMI), total energy intake, current smoking, statin treatment and diabetes. We also evaluated the effect modification by folate status and statin treatment in these linear regression analyses. Results: Median dietary betaine intake in this cohort was 134 mg/d. The participants (80.4% males) had a median age of 62 years. Unadjusted Spearman correlation analyses revealed a significant positive association of dietary betaine intake...
2015-05-15T00:00:00ZFood intake and weight changes in Norwegian hip fracture patientshttp://hdl.handle.net/1956/11676
Food intake and weight changes in Norwegian hip fracture patients
Ådnanes, Svanhild
Master thesis
Background: Norway has the highest rates of hip fractures
worldwide. Hip fracture patients represent a vulnerable group
with high mortality and morbidity after one year, and as the
elderly population is increasing a consecutive increase in hip
fractures is expected. Energy and protein requirements are
increased during disease and inflammatory state, and muscle
wasting can be expected in bedridden patients. The poor
nutritional status in hip fracture patients is increasingly
recognized, however, little is known about food intake and
weight changes in the immediate postoperative period in
Norwegian patients.
Objective: To investigate energy and protein intake and weight
development during the acute and rehabilitation phase after a
hip fracture in Norwegian patients, and to consider the patients
nutritional risk.
Methods: Forty patients were recruited to the study during
hospitalization for hip fracture, and were investigated at hospital
(median 3 days after surgery), at a rehabilitation unit (median 15
days after surgery) and at home (median 63 days after surgery).
Energy and protein intake, weight, mid-upper arm circumference
and triceps skinfold were collected at all visits. Nutritional risk
screening, new mobility score, bioelectrical impedance analysis,
handgrip and quadriceps strength were carried out at the
rehabilitation unit/ at the home of the patients.
Results: We found a very low energy and protein intake at
hospital where no patients reached their estimated
requirements, and an improved, but still insufficient energy and
protein intake at rehabilitation and at home. Eleven out of 14
patients lost weight from hospital to rehabilitation (median for
the group was -2.9 kg, p = 0.048) and eight out of 12 patients
lost weight from hospital to home (median for the groups was
-2.2 kg, p = 0.147). Eighty percent of the patients were in
nutritional risk at the rehabilitation stay. Due to the small number
of patients and the high drop-out rate, most findings did not
achieve statistical significance, and therefore the results have to
be interpreted with care.
Conclusion: In conclusion, energy and protein intake was very
low in hospitalised hip fracture patients, and remained sub-
optimal during rehabilitation and after returning home. A
significant weight loss and a high number of patients in
nutritional risk, suggest that the patients in the present study
experienced a critical phase, and this issue should be
investigated further.
2015-05-15T00:00:00ZPsychiatric Comorbidity, Social Aspects and Quality of Life in a Population-Based Cohort of Expecting Fathers with Epilepsyhttp://hdl.handle.net/1956/11655
Psychiatric Comorbidity, Social Aspects and Quality of Life in a Population-Based Cohort of Expecting Fathers with Epilepsy
Reiter, Simone B. C. Frizell; Veiby, Gyri; Bjørk, Marte Helene; Engelsen, Bernt; Daltveit, Anne Kjersti; Gilhus, Nils Erik
Journal article
<p>Objectives. To investigate psychiatric disorders, adverse social aspects and quality of life in men with epilepsy during partner’s pregnancy.</p>
<p>Method.
We used data from the Norwegian Mother and Child Cohort Study, including 76,335 men with pregnant partners. Men with epilepsy were compared to men without epilepsy, and to men with non-neurological chronic diseases.</p>
<p>Results.
Expecting fathers in 658 pregnancies (mean age 31.8 years) reported a history of epilepsy, 36.9% using antiepileptic drugs (AEDs) at the onset of pregnancy. Symptoms of anxiety or depression were increased in epilepsy (7.0% and 3.9%, respectively) vs. non-epilepsy (4.6% and 2.5%, respectively, p = 0.004 and 0.023), and so were new onset symptoms of depression (2.0% vs. 1.0%, p < 0.031) and anxiety (4.3% vs. 2.3%, p = 0.023). Low self-esteem (2.5%) and low satisfaction with life (1.7%) were more frequent among fathers with epilepsy compared to fathers without epilepsy (1.3% and 0.7%, respectively, p = 0.01 and 0.010). Adverse social aspects and life events were associated with epilepsy vs. both reference groups. Self-reported diagnoses of ADHD (2.2%) and bipolar disorder (1.8%) were more common in epilepsy vs. non-epilepsy (0.4% and 0.3%, respectively, p = 0.002 and 0.003) and non-neurological chronic disorders (0.5% and 0.5%, respectively, p = 0.004 and 0.018). A screening tool for ADHD symptoms revealed a higher rate compared to self-reported ADHD (9.5% vs. 2.2%, p < 0.001).</p>
<p>Conclusion.
Expecting fathers with epilepsy are at high risk of depression and anxiety, adverse socioeconomic aspects, low self-esteem, and low satisfaction with life. Focus on mental health in fathers with epilepsy during and after pregnancy is important. The use of screening tools can be particularly useful to identify those at risk.</p>
2015-12-04T00:00:00ZInflammation markers in multiple sclerosis: CXCL16 reflects and may also predict disease activityhttp://hdl.handle.net/1956/11654
Inflammation markers in multiple sclerosis: CXCL16 reflects and may also predict disease activity
Holmøy, Trygve; Løken-Amsrud, Kristin Ingeleiv; Bakke, Jacob; Beiske, Antonie Giæver; Bjerve, Kristian S; Hovdal, Harald Olav; Lilleås, Finn; Midgard, Rune; Pedersen, Tom; Saltyte Benth, Jurate; Torkildsen, Øivind; Wergeland, Stig; Myhr, Kjell-Morten; Michelsen, Annika; Aukrust, Pål; Ueland, Thor
Journal article
<p>Background. Serum markers of inflammation are candidate biomarkers in multiple sclerosis (MS). ω-3 fatty acids are suggested to have anti-inflammatory properties that might be beneficial in MS. We aimed to explore the relationship between serum levels of inflammation markers and MRI activity in patients with relapsing remitting MS, as well as the effect of ω-3 fatty acids on these markers.</p>
<p>Methods. We performed a prospective cohort study in 85 relapsing remitting MS patients who participated in a randomized clinical trial of ω-3 fatty acids versus placebo (the OFAMS study). During a period of 24 months 12 repeated magnetic resonance imaging (MRI) scans and nine serum samples were obtained. We measured 10 inflammation markers, including general down-stream markers of inflammation, specific markers of up-stream inflammatory pathways, endothelial action, and matrix regulation.</p>
<p>Results. After Bonferroni correction, increasing serum levels of CXCL16 and osteoprotegerin were associated with low odds ratio for simultaneous MRI activity, whereas a positive association was observed for matrix metalloproteinase (MMP) 9. CXCL16 were also associated with low MRI activity the next month, but this was not significant after Bonferroni correction. In agreement with previously reported MRI and clinical results, ω-3 fatty acid treatment did not induce any change in the inflammation markers.</p>
<p>Conclusions. Serum levels of CXCL16, MMP-9, and osteoprotegerin reflect disease activity in MS, but are not affected by ω-3 fatty acid treatment. CXCL16 could be a novel biomarker and potential predictor of disease activity in MS.</p>
2013-09-19T00:00:00ZAlpha-tocopherol and MRI outcomes in multiple sclerosis - association and predictionhttp://hdl.handle.net/1956/11639
Alpha-tocopherol and MRI outcomes in multiple sclerosis - association and prediction
Løken-Amsrud, Kristin Ingeleiv; Myhr, Kjell-Morten; Bakke, Søren Jacob; Beiske, Antonie Giæver; Bjerve, Kristian S; Bjørnarå, Bård T.; Hovdal, Harald Olav; Lilleås, Finn; Midgard, Rune; Pedersen, Tom; Saltyte Benth, Jurate; Torkildsen, Øivind; Wergeland, Stig; Holmøy, Trygve
Journal article
<p>Objective: Alpha-tocopherol is the main vitamin E compound in humans, and has important antioxidative and immunomodulatory properties. The aim of this study was to study alpha-tocopherol concentrations and their relationship to disease activity in Norwegian multiple sclerosis (MS) patients.</p>
<p>Methods: Prospective cohort study in 88 relapsing-remitting MS (RRMS) patients, originally included in a randomised placebo-controlled trial of omega-3 fatty acids (the OFAMS study), before and during treatment with interferon beta. The patients were followed for two years with repeated 12 magnetic resonance imaging (MRI) scans and nine serum measurements of alpha-tocopherol.</p>
<p>Results: During interferon beta (IFNB) treatment, each 10 &micro;mol/L increase in alpha-tocopherol reduced the odds (CI 95%) for simultaneous new T2 lesions by 36.8 (0.5&ndash;59.8) %, p = 0.048, and for combined unique activity by 35.4 (1.6&ndash;57.7) %, p = 0.042, in a hierarchical regression model. These associations were not significant prior to IFNB treatment, and were not noticeably changed by gender, age, body mass index, HLA-DRB1*15, treatment group, compliance, or the concentrations of 25-hydroxyvitamin D, retinol, neutralising antibodies against IFNB, or the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid. The corresponding odds for having new T1 gadolinium enhancing lesions two months later was reduced by 65.4 (16.5&ndash;85.7) %, p = 0.019, and for new T2 lesions by 61.0 (12.4&ndash;82.6) %, p = 0.023.</p>
<p>Conclusion: During treatment with IFNB, increasing serum concentrations of alpha-tocopherol were associated with reduced odds for simultaneous and subsequent MRI disease activity in RRMS patients.</p>
2013-01-22T00:00:00ZGenetic and hypoxic alterations of the microRNA-210-ISCU1/2 axis promote iron-sulfur deficiency and pulmonary hypertensionhttp://hdl.handle.net/1956/11632
Genetic and hypoxic alterations of the microRNA-210-ISCU1/2 axis promote iron-sulfur deficiency and pulmonary hypertension
White, Kevin; Lu, Yu; Annis, Sofia; Hale, Andrew E.; Chau, B. Nelson; Dahlman, James E.; Hemann, Craig; Opotowsky, Alexander R.; Vargas, Sara O.; Rosas, Ivan; Perrella, Mark A.; Osorio, Juan C.; Haley, Kathleen J.; Graham, Brian B.; Kumar, Rahul; Saggar, Rajan; Saggar, Rajeev; Wallace, W. Dean; Ross, David J.; Khan, Omar F.; Bader, Andrew; Gochuico, Bernadette R.; Matar, Majed; Polach, Kevin; Johannessen, Nicolai; Prosser, Haydn M.; Anderson, Daniel G.; Langer, Robert; Zweier, Jay L.; Bindoff, Laurence; Systrom, David; Waxman, Aaron B.; Jin, Richard C.; Chan, Stephen Y.
Journal article
Iron–sulfur (Fe‐S) clusters are essential for mitochondrial metabolism, but their regulation in pulmonary hypertension (PH) remains enigmatic. We demonstrate that alterations of the miR‐210‐ISCU1/2 axis cause Fe‐S deficiencies in vivo and promote PH. In pulmonary vascular cells and particularly endothelium, hypoxic induction of miR‐210 and repression of the miR‐210 targets ISCU1/2 down‐regulated Fe‐S levels. In mouse and human vascular and endothelial tissue affected by PH, miR‐210 was elevated accompanied by decreased ISCU1/2 and Fe‐S integrity. In mice, miR‐210 repressed ISCU1/2 and promoted PH. Mice deficient in miR‐210, via genetic/pharmacologic means or via an endothelial‐specific manner, displayed increased ISCU1/2 and were resistant to Fe‐S‐dependent pathophenotypes and PH. Similar to hypoxia or miR‐210 overexpression, ISCU1/2 knockdown also promoted PH. Finally, cardiopulmonary exercise testing of a woman with homozygous ISCU mutations revealed exercise‐induced pulmonary vascular dysfunction. Thus, driven by acquired (hypoxia) or genetic causes, the miR‐210‐ISCU1/2 regulatory axis is a pathogenic lynchpin causing Fe‐S deficiency and PH. These findings carry broad translational implications for defining the metabolic origins of PH and potentially other metabolic diseases sharing similar underpinnings.
2015-01-01T00:00:00ZUrinary proteomics in chronic kidney disease: diagnosis and risk of progression beyond albuminuriahttp://hdl.handle.net/1956/11627
Urinary proteomics in chronic kidney disease: diagnosis and risk of progression beyond albuminuria
Øvrehus, Marius Altern; Zürbig, Petra; Vikse, Bjørn Egil; Hallan, Stein
Journal article
<p>Background: The contrast between a high prevalence of chronic kidney disease (CKD) and the low incidence of end-stage renal disease highlights the need for new biomarkers of progression beyond albuminuria testing. Urinary proteomics is a promising method, but more studies focusing on progression rate and patients with hypertensive nephropathy are needed.</p>
<p>Results: We analyzed urine samples with capillary electrophoresis coupled to a mass-spectrometer from 18 well characterized patients with CKD stage 4&ndash;5 (of whom six with hypertensive nephropathy) and 17 healthy controls. Classification scores based on a previously developed panel of 273 urinary peptides were calculated and compared to urine albumin dipstick results. Urinary proteomics classified CKD with a sensitivity of 0.95 and specificity of 1.00. Overall diagnostic accuracy (area under ROC curve) was 0.98, which was better than for albuminuria (0.85, p = 0.02). Results for hypertensive nephropathy were similar to other CKD diagnoses. Adding the proteomic score to an albuminuria model improved detection of rapid kidney function decline (&gt;4 ml/min/1.73 m2 per year) substantially: area under ROC curve increased from 0.762 to 0.909 (p = 0.042), and 38% of rapid progressors were correctly reclassified to a higher risk and 55% of slow progressors were correctly reclassified to a lower risk category. Reduced excretion of collagen types I&ndash;III, uromodulin, and other indicators of interstitial inflammation, fibrosis and tubular dysfunction were associated with CKD diagnosis and rapid progression. Patients with hypertensive nephropathy displayed the same findings as other types of CKD.</p>
<p>Conclusions: Urinary proteomic analyses had a high diagnostic accuracy for CKD, including hypertensive nephropathy, and strongly improved identification of patients with rapid kidney function decline beyond albuminuria testing.</p>
2015-08-07T00:00:00ZPhysicians’ use of pain scale and treatment procedures among children and youth in emergency primary care - a cross sectional studyhttp://hdl.handle.net/1956/11490
Physicians’ use of pain scale and treatment procedures among children and youth in emergency primary care - a cross sectional study
Moutte, Svein-Denis; Brudvik, Christina; Morken, Tone
Journal article
<p>Background: Pain is a common symptom in children and youth attending casualty centres and emergency departments. The aim of this study was to acquire more knowledge about how pain in children is measured and handled by emergency primary care physicians.</p>
<p>Methods: A structured questionnaire study was performed among 75 emergency primary care physicians in a Norwegian accident and emergency department (AED). We used descriptive statistics to analyse the use of a pain scale, the use of weight and age when dosing pain medication, the need for more knowledge and the need for pain management procedures in children. The Pearson chi-square test was used to analyse differences between groups.</p>
<p>Results: A pain scale with a visual analogue scale (VAS) had been used by 59 % of physicians in young patients aged 9 to 19 years, by 23 % in children aged 3 to 8 years, and by 3 % in children below 3 years. A total of 63 % of physicians reported that they used the child&rsquo;s weight instead of the age interval when estimating the needed dose of painkillers. They relied on parents&rsquo; weight estimation and seldom measured the child&rsquo;s weight at attendance. Most emergency medical care physicians reported a need for more knowledge and better procedures related to both pain evaluation and pain treatment in children and youth. The physicians included in the study were demographically representative of AED physicians in Norway (average age 37 years old, 55 % men, 76 % had studied medicine in Norway and 49 % had fewer than 5 years of medical experience).</p>
<p>Conclusions: Emergency primary care physicians report a need for pain assessment procedures in children and youth. They sometimes use a pain scale when measuring and managing pain in patients aged 9 to 19 years, but seldom in younger patients.</p>
2015-11-06T00:00:00ZLong-term follow-up and survivorship after completing systematic surveillance in stage I–III colorectal cancer: who is still at risk?http://hdl.handle.net/1956/11458
Long-term follow-up and survivorship after completing systematic surveillance in stage I–III colorectal cancer: who is still at risk?
Veen, Torhild; Stormark, Kjartan; Nedrebø, Bjørn Steinar Olden; Berg, Marianne; Søreide, Jon Arne; Kørner, Hartwig; Søreide, Kjetil
Journal article
<p>Purpose: In patients with a high life expectancy at the time of surgery for colorectal cancer (CRC), the long-term outcome may be influenced by factors other than their cancer. We aimed to investigate the long-term outcome and cause of death beyond a 5-year surveillance programme.</p>
<p>Methods: We evaluated the overall survival (OS) and cancer-specific survival (CSS) of a population-based cohort of stage I&ndash;III CRC patients &lt;75 years old who completed a systematic surveillance programme.</p>
<p>Results: In total, 161 patients &lt;75 years old, 111 (69 %) of whom were node negative (pN0), were included. The median follow-up time was 12.1 years. The OS was 54 % at 15 years and differed significantly between the pN0 and pN+ patients (65 vs. 30 %; P&thinsp;&lt;&thinsp;0.001); CSS (72 %) also differed between the pN0 and pN+ patients (85 vs. 44 %; P&thinsp;&lt;&thinsp;0.001). For the 5-year survivors (n&thinsp;=&thinsp;119), 14 (12 %) died of CRC during additional long-term follow-up (7 each for pN0 and pN+), and 6 patients (5 %; all pN0) died of other cancers. Patients aged &lt;65 years exhibited better long-term survival (81 %), but most of the deaths were due to CRC (10/12 deaths). Only two of the 14 cancer-related deaths involved microsatellite instable (MSI) CRC. Females exhibited better OS and CSS beyond 5 years of surveillance.</p>
<p>Conclusions: The long-term survival beyond 5-year survivorship for stage I&ndash;III CRC is very good. Nonetheless, cancer-related deaths are encountered in one-third of patients and occur most frequently in patients who are &lt;65 years old at disease onset&mdash;pointing to a still persistent risk several years after surgery.</p>
2015-09-01T00:00:00ZLong term clinical disease progression in patients with Parkinson’s disease after STN Deep Brain Stimulationhttp://hdl.handle.net/1956/11457
Long term clinical disease progression in patients with Parkinson’s disease after STN Deep Brain Stimulation
Lilleeng, Bård Flattun
Doctoral thesis
<p>Background: Parkinson&rsquo;s disease (PD) is a progressive neurodegenerative disorder with severe longterm impact on patients, their caregivers and on the society in general [1]. The treatment of PD is symptomatic. Surgical treatment with chronic high frequency stimulation of the subthalamic nuclei (STN-DBS) has been shown to provide long term symptom relief with few complications in selected patients with PD [2-4].</p>
<p>Aim: The aim of the thesis has been to elucidate the long-term effects of STN-DBS on the development of clinical symptoms in PD.</p>
<p>Materials and methods: All PD patients treated with STN-DBS between 2001-2007 at Rikshospitalet (N=144) and at Stavanger University Hospital (N=28) were prospectively followed with standardized examinations, and all 172 STN-DBS operated PD patients were included in the scientific material for the thesis. As reference we used the patients from a population-based prevalence study conducted with patient recruitment between September 1992 and May 1993, before STN-DBS was available.</p>
<p>Results: We confirm that STN-DBS surgery can be performed with good and stable long time results on dopaminergic motor symptoms. Perioperative mortality was low and the rate of major adverse events low. The non-motor features of PD seem to develop independently of intervention with STN-DBS, as do FOG and falls. Fatigue is observed to develop at a high rate in STN-DBS operated patients after the first year postoperatively.</p>
<p>Conclusions and implications: STN-DBS is a very good treatment option for motor symptoms in selected patients with advanced PD. The benefits of the treatment are limited to motor symptom control as the underlying PD pathology continues to develop in operated patients similar to the natural history of PD. Fatigue seem to develop at a high rate in STN-DBS operated patients after the first year postoperatively. Our findings are relevant to advising patients both about the indication for, and the timing of, STN-DBS surgery in PD</p>
2016-02-12T00:00:00ZIncreased risk of revision of cementless stemmed total hip arthroplasty with metal-on-metal bearingsData from the Nordic Arthroplasty Register Associationhttp://hdl.handle.net/1956/11429
Increased risk of revision of cementless stemmed total hip arthroplasty with metal-on-metal bearingsData from the Nordic Arthroplasty Register Association
Varnum, Claus; Pedersen, Alma B; Mäkelä, Keijo; Eskelinen, Antti; Havelin, Leif Ivar; Furnes, Ove; Kärrholm, Johan; Garellick, Göran; Overgaard, Søren
Journal article
<p>Background and purpose &mdash; Data from the national joint registries in Australia and England and Wales have revealed inferior medium-term survivorship for metal-on-metal (MoM) total hip arthroplasty (THA) than for metal-on-polyethylene (MoP) THA. Based on data from the Nordic Arthroplasty Register Association (NARA), we compared the revision risk of cementless stemmed THA with MoM and MoP bearings and we also compared MoM THA to each other.</p>
<p>Patients and methods &mdash; We identified 32,678 patients who were operated from 2002 through 2010 with cementless stemmed THA with either MoM bearings (11,567 patients, 35%) or MoP bearings (21,111 patients, 65%). The patients were followed until revision, death, emigration, or the end of the study period (December 31, 2011), and median follow-up was 3.6 (interquartile range (IQR): 2.4&ndash;4.8) years for MoM bearings and 3.4 (IQR: 2.0&ndash;5.8) years for MoP bearings. Multivariable regression in the presence of competing risk of death was used to assess the relative risk (RR) of revision for any reason (with 95% confidence interval (CI)).</p>
<p>Results &mdash; The cumulative incidence of revision at 8 years of follow-up was 7.0% (CI: 6.0&ndash;8.1) for MoM bearings and 5.1% (CI: 4.7&ndash;5.6) for MoP bearings. At 6 years of follow-up, the RR of revision for any reason was 1.5 (CI: 1.3&ndash;1.7) for MoM bearings compared to MoP bearings. The RR of revision for any reason was higher for the ASR (adjusted RR = 6.4, CI: 5.0&ndash;8.1), the Conserve Plus (adjusted RR = 1.7, CI: 1.1&ndash;2.5) and &ldquo;other&rdquo; acetabular components (adjusted RR = 2.4, CI: 1.5&ndash;3.9) than for MoP THA at 6 years of follow-up.</p>
<p>Interpretation &mdash; At medium-term follow-up, the survivorship for cementless stemmed MoM THA was inferior to that for MoP THA, and metal-related problems may cause higher revision rates for MoM bearings with longer follow-up.</p>
2015-01-01T00:00:00ZThe risk of revision in total knee arthroplasty is not affected by previous high tibial osteotomyhttp://hdl.handle.net/1956/11420
The risk of revision in total knee arthroplasty is not affected by previous high tibial osteotomy
Badawy, Mona; Fenstad, Anne Marie; Indrekvam, Kari; Havelin, Leif Ivar; Furnes, Ove
Journal article
<p>Background and purpose &mdash; Previous studies have found different outcomes after revision of knee arthroplasties performed after high tibial osteotomy (HTO). We evaluated the risk of revision of total knee arthroplasty with or without previous HTO in a large registry material.</p>
<p>Patients and methods &mdash; 31,077 primary TKAs were compared with 1,399 TKAs after HTO, using Kaplan-Meier 10-year survival percentages and adjusted Cox regression analysis.</p>
<p>Results &mdash; The adjusted survival analyses showed similar survival in the 2 groups. The Kaplan-Meier 10-year survival was 93.8% in the primary TKA group and 92.6% in the TKA-post-HTO group. Adjusted RR was 0.97 (95% CI: 0.77&ndash;1.21; p = 0.8).</p>
<p>Interpretation &mdash; In this registry-based study, previous high tibial osteotomy did not appear to compromise the results regarding risk of revision after total knee arthroplasty compared to primary knee arthroplasty.</p>
2015-01-01T00:00:00ZBetter survival of hybrid total knee arthroplasty compared to cemented arthroplasty.http://hdl.handle.net/1956/11418
Better survival of hybrid total knee arthroplasty compared to cemented arthroplasty.
Petursson, Gunnar; Fenstad, Anne Marie; Havelin, Leif Ivar; Gøthesen, Øystein; Lygre, Stein Håkon Låstad; Röhrl, Stephan Maximillian; Furnes, Ove
Journal article
<p>Background and purpose &mdash; There have been few comparative studies on total knee replacement (TKR) with cemented tibia and uncemented femur (hybrid TKR). Previous studies have not shown any difference in revision rate between cemented and hybrid fixation, but these studies had few hybrid prostheses. We have evaluated the outcome of hybrid TKR based on data from the Norwegian Arthroplasty Register (NAR).</p>
<p>Patients and methods &mdash; We compared 4,585 hybrid TKRs to 20,095 cemented TKRs with risk of revision for any cause as the primary endpoint. We included primary TKRs without patella resurfacing that were reported to the NAR during the years 1999&ndash;2012. To minimize the possible confounding effect of prosthesis brands, only brands that were used both as hybrids and cemented in more than 200 cases were included. Kaplan-Meier survival analysis and Cox regression analysis were done with adjustment for age, sex, and preoperative diagnosis. To include death as a competing risk, cumulative incidence function estimates were calculated.</p>
<p>Results &mdash; Estimated survival at 11 years was 94.3% (95% CI: 93.9&ndash;94.7) in the cemented TKR group and 96.3% (CI: 95.3&ndash;97.3) in the hybrid TKR group. The adjusted Cox regression analysis showed a lower risk of revision in the hybrid group (relative risk = 0.58, CI: 0.48&ndash;0.72, p &lt; 0.001). The hybrid group included 3 brands of prostheses: LCS classic, LCS complete, and Profix. Profix hybrid TKR had lower risk of revision than cemented TKR, but the LCS classic and LCS complete did not. Kaplan-Meier estimated survival at 11 years was 96.8% (CI: 95.6&ndash;98.0) in the hybrid Profix group and 95.2% (CI: 94.6&ndash;95.8) in the cemented Profix group. Mean operating time was 17 min longer in the cemented group.</p>
<p>Interpretation &mdash; Survivorship of the hybrid TKR at 11 years was better than that for cemented TKR, or the same, depending on the brand of prosthesis. Hybrid fixation appears to be a safe and time-efficient alternative to cemented fixation in total knee replacement surgery.</p>
2015-01-01T00:00:00ZIncreased risk of revision for infection in rheumatoid arthritis patients with total hip replacements. A study of 390,671 primary arthroplasties from the Nordic Arthroplasty Register Associationhttp://hdl.handle.net/1956/11390
Increased risk of revision for infection in rheumatoid arthritis patients with total hip replacements. A study of 390,671 primary arthroplasties from the Nordic Arthroplasty Register Association
Schrama, Johannes Cornelis; Fenstad, Anne Marie; Dale, Håvard; Hallan, Geir; Overgaard, Søren; Pedersen, Alma B; Kärrholm, Johan; Garellick, Göran; Pulkkinen, Pekka; Eskelinen, Antti; Mäkelä, Keijo; Engesæter, Lars B.; Fevang, Bjørg-Tilde
Journal article
<p>Background and purpose &mdash; Medical treatment of rheumatoid arthritis (RA) has changed dramatically over the last 15 years, including immune modulation. We investigated the risk of revision for infection after primary total hip replacement (THR) in patients with rheumatoid arthritis over a 16-year period, and compared it with that in THR patients with osteoarthritis (OA).</p>
<p>Patients and methods &mdash; We identified 13,384 THRs in RA patients and 377,287 THRs in OA patients from 1995 through 2010 in a dataset from the Nordic Arthroplasty Register Association (NARA). Kaplan-Meier survival curves, with revision for infection as the endpoint, were constructed. Cox regression analyses were performed to calculate the relative risk (RR) of revision for infection adjusted for age, sex, fixation technique, and year of primary surgery.</p>
<p>Results &mdash; RA patients had a 1.3 times (95% CI 1.0&ndash;1.6) higher risk of revision for infection. After 2001, this risk increased more for RA patients than for OA patients. During the first 3 months and from 8 years postoperatively, the risk of revision for infection was higher in RA patients with THRs fixated with antibiotic-loaded cement than in corresponding OA patients.</p>
<p>Interpretation &mdash; We found a slightly higher overall risk of revision for infection in RA patients than in OA patients, but this difference was only present after 2001. In THRs with antibiotic-loaded cement, the risk of very early and late infections leading to revision was higher in RA patients than in OA patients.</p>
2015-01-01T00:00:00ZObstetric anal sphincter injuries. A population-based study of improvement of carehttp://hdl.handle.net/1956/11388
Obstetric anal sphincter injuries. A population-based study of improvement of care
Rygh, Astrid
Doctoral thesis
<p>Background: Obstetric anal sphincter injuries (OASIS) are tears of the anal sphincters, eventually also involving the rectum, sustained during vaginal birth, and 30% to 50% of women experience anal incontinence (AI) after OASIS, which is the main cause of AI in younger women. Furthermore, increasing OASIS rates were observed in Norway and other countries during the last decades. There was a strong need for improved sphincter repairs in order to reduce the morbidity after OASIS and for effective preventive measures. The Norwegian health authorities launched an action plan in 2006 aiming to reduce the OASIS rates. The plan included an interventional study of implementation of “hands-on” manual perineal support during the expulsive phase of labour, in which our department participated.</p> <p>Aims: We aimed to compare the overlap technique and the traditional end-to-end approximation technique for the primary repair of OASIS with regard to faecal incontinence. Further, to investigate the association of oxytocin augmentation of labour with OASIS in a model of risk factors exerting their effect during the active, second stage of labour. Finally, to assess the impact of changes in clinical management on the prevalence of OASIS, and on risk factors associated with OASIS, from 2001 through 2012 in the unselected obstetric population of Stavanger University Hospital (SUS).</p> <p>Participants and methods: We included 119 women who sustained OASIS at SUS between 2005 and 2007 in a randomised controlled trial (RCT) comparing the overlap technique with the traditional end-to-end repair for OASIS. After one year the participants were evaluated regarding anal incontinence, and endoanal ultrasonographic (EAUS) and anal manometry findings (paper one). We used consecutively registered, departemental data for the population-based studies of the associations between oxytocin augmentation and OASIS and for trends of OASIS and risk factors (paper two and three). The study populations comprised nulliparous women with a single, cephalic, term pregnancy and spontaneous labour, who delivered vaginally. We developed a dynamic, statistical model of risk factors on the causal pathway to OASIS for use in both studies. Based on the presence or absence of oxytocin augmentation, episiotomy, instrumental delivery and birthweigth &lt;4000 g/≥4000 g we modelled in logistic regression the best fit for the prediction of OASIS.</p> <p>Results: The overlap and the end-to-end repair techniques were similar for all outcomes at the twelve month follow-up, which was attended by 101 out of the 119 participants. Overall, two women suffered from faecal incontinence, and 15% had AI as defined by Wexner score (paper one). Oxytocin augmentation was associated with aOR 1.8 (95%CI 1.5 – 2.2) for OASIS in spontaneous births of normal-sized infants among 15 476 nulliparous women between 1999 and 2012 (paper two). Episiotomy was associated with lower OASIS rates in instrumental, but not in spontaneous births. We found important effect modification between the predictors of OASIS. In the population of 14 479 nulliparous women of the overall OASIS rate declined from 9.8% to 2.9% between 2001 and 2012; from 6.5% to 2.2% in normal deliveries, and from 15.1% to 3.0% in instrumental deliveries when episiotomy was applied (paper three). The change was mainly explained by the implementation of the ”hands-on” perineal support concept, and the recommendation of a routine, lateral episiotomy for instrumental deliveries from 2007. The distribution of the study population changed in line with our revised guidelines, which also included implementation of the WHO partogram and a restricted use of oxytocin augmentation.</p> <p>Conclusions: The randomised study of repair techniques for OASIS did not support a recommendation of one repair method over the other. Better outcomes after OASIS than previously reported seem possible following training in anatomical sphincter repairs. We found an association of oxytocin augmentation with higher OASIS rates in the large population of nulliparous women having normal births. The ”hands-on” management, and the routine use of a lateral episiotomy for instrumental births were associated with significantly lower OASIS rates. It is important to consider the interaction of factors associated with OASIS.</p>
2015-12-11T00:00:00ZCombined endorectal ultrasonography and strain elastography for the staging of early rectal cancerhttp://hdl.handle.net/1956/11385
Combined endorectal ultrasonography and strain elastography for the staging of early rectal cancer
Waage, Jo Erling Riise; Bach, Simon; Pfeffer, Frank; Leh, Sabine Maria; Havre, Roald Flesland; Ødegaard, Svein; Baatrup, Gunnar
Journal article
<p>Aim: Strain elastography is a novel approach to rectal tumour evaluation. The primary aim of this study was to correlate elastography to pT stages of rectal tumours and to assess the ability of the method to differentiate rectal adenomas (pT0) from early rectal cancer (pT1&ndash;2). Secondary aims were to compare elastography with endorectal ultrasonography (ERUS) and to propose a combined strain elastography and ERUS staging algorithm.</p>
<p>Method: In all, 120 consecutive patients with a suspected rectal tumour were examined in this staging study. Patients receiving surgery without neoadjuvant radiotherapy were included (n = 59). All patients were examined with ERUS and elastography. Treatment decisions were made by multidisciplinary team (MDT) assessment, without considering the strain elastography examination.</p>
<p>Results: Histopathology identified 21 adenomas, 13 pT1, 9 pT2, 15 pT3 and one pT4. Mean elastography strain ratios were predictive of T stage (P = 0.01). Differentiation of adenomas from early rectal cancer (pT1&ndash;2) had sensitivity, specificity and accuracy of 0.82, 0.86 and 0.84 for elastography and 0.82, 0.62 and 0.72 for ERUS. A combined staging algorithm was developed to identify tumours eligible for local resection. Based on MDT evaluation 32% of tumours later identified as pT0 or pT1 were treated with total mesorectal excision, even though a local excision might have sufficed. Combined ERUS and elastography evaluation would have significantly reduced this number to 9% (P = 0.008).</p>
<p>Conclusion: Elastography may improve the staging of adenomas and early rectal cancer compared with ERUS alone. Combined ERUS and elastography assessment is likely to further improve the selection of patients for local resection.</p>
2015-01-01T00:00:00ZPhotopic full-field electroretinography and optical coherence tomography in type 1 diabetic retinopathyhttp://hdl.handle.net/1956/11360
Photopic full-field electroretinography and optical coherence tomography in type 1 diabetic retinopathy
Jansson, Ragnhild Wivestad; Ræder, Maria B.; Krohn, Jørgen Gitlesen
Journal article
<p>Purpose: The purpose of this study was to evaluate the role of photopic full-field electroretinography (ERG) and retinal thickness measurements by spectral-domain optical coherence tomography (SD-OCT) in the assessment of disease severity in type 1 diabetic retinopathy.</p>
<p>Methods: A population-based cohort of 151 patients with type 1 diabetes underwent a complete ophthalmic examination, including photopic full-field ERG and SD-OCT for retinal thickness measurements. Stereoscopic fundus photographs were taken according to the Early Treatment Diabetic Retinopathy Study protocol, and the classification of diabetic retinopathy was based on the International Clinical Diabetic Retinopathy Disease Severity Scale. Associations between photographically determined retinopathy level, b-wave amplitude and peak time of the photopic single-flash and 30-Hz flicker ERG, and central retinal thickness parameters were evaluated.</p>
<p>Results: For all ERG measurements, the amplitude decreased and peak time increased with progression of the disease, but these associations lost statistical significance after adjusting for age and excluding laser-treated patients. Mean retinal thickness was significantly associated with the b-wave amplitude of photopic single-flash and 30-Hz flicker responses (r2&thinsp;=&thinsp;0.08, p&thinsp;=&thinsp;0.006; and r2&thinsp;=&thinsp;0.05, p&thinsp;=&thinsp;0.025, respectively), but revealed no association with retinopathy level.</p>
<p>Conclusions: Photopic full-field ERG and SD-OCT-derived retinal thickness parameters have limited clinical value in the staging of diabetic retinopathy. However, thinning of the central retina leads to significant functional impairment and may reflect an ongoing neurodegenerative process in the retinal tissue.</p>
2015-07-01T00:00:00ZTiming of use of cod liver oil, a vitamin D source, and multiple sclerosis risk: The EnvIMS study.http://hdl.handle.net/1956/11286
Timing of use of cod liver oil, a vitamin D source, and multiple sclerosis risk: The EnvIMS study.
Cortese, Marianna; Riise, Trond; Bjørnevik, Kjetil Lauvland; Holmøy, Trygve; Kampman, Margitta Theodora; Magalhaes, Sandra; Pugliatti, Maura; Wolfson, Christina; Myhr, Kjell-Morten
Journal article
<p>Background: Low vitamin D levels have been associated with an increased risk of multiple sclerosis (MS), although it remains unknown whether this relationship varies by age.</p>
<p>Objective: The objective of this paper is to investigate the association between vitamin D3 supplementation through cod liver oil at different postnatal ages and MS risk.</p>
<p>Methods: In the Norwegian component of the multinational case-control study Environmental Factors In Multiple Sclerosis (EnvIMS), a total of 953 MS patients with maximum disease duration of 10 years and 1717 controls reported their cod liver oil use from childhood to adulthood.</p>
<p>Results: Self-reported supplement use at ages 13&ndash;18 was associated with a reduced risk of MS (OR 0.67, 95% CI 0.52&ndash;0.86), whereas supplementation during childhood was not found to alter MS risk (OR 1.01, 95% CI 0.81&ndash;1.26), each compared to non-use during the respective period. An inverse association was found between MS risk and the dose of cod liver oil during adolescence, suggesting a dose-response relationship (p trend = 0.001) with the strongest effect for an estimated vitamin D3 intake of 600&ndash;800 IU/d (OR 0.46, 95% CI 0.31&ndash;0.70).</p>
<p>Conclusions: These findings not only support the hypothesis relating to low vitamin D as a risk factor for MS, but further point to adolescence as an important susceptibility period for adult-onset MS.</p>
2015-01-01T00:00:00ZMolecular subtypes in stage II-III colon cancer defined by genomic instability: Early recurrence-risk associated with a high copy-number variation and loss of RUNX3 and CDKN2Ahttp://hdl.handle.net/1956/11056
Molecular subtypes in stage II-III colon cancer defined by genomic instability: Early recurrence-risk associated with a high copy-number variation and loss of RUNX3 and CDKN2A
Berg, Marianne; Nordgård, Oddmund; Kørner, Hartwig; Oltedal, Satu; Smaaland, Rune; Søreide, Jon Arne; Søreide, Kjetil
Journal article
<p>Objective: We sought to investigate various molecular subtypes defined by genomic instability that may be related to early death and recurrence in colon cancer.</p>
<p>Methods: We sought to investigate various molecular subtypes defined by instability at microsatellites (MSI), changes in methylation patterns (CpG island methylator phenotype, CIMP) or copy number variation (CNV) in 8 genes. Stage II-III colon cancers (n = 64) were investigated by methylation-specific multiplex ligated probe amplification (MS-MLPA). Correlation of CNV, CIMP and MSI, with mutations in KRAS and BRAFV600E were assessed for overlap in molecular subtypes and early recurrence risk by uni- and multivariate regression.</p>
<p>Results: The CIMP phenotype occurred in 34% (22/64) and MSI in 27% (16/60) of the tumors, with noted CIMP/MSI overlap. Among the molecular subtypes, a high CNV phenotype had an associated odds ratio (OR) for recurrence of 3.2 (95% CI 1.1-9.3; P = 0.026). Losses of CACNA1G (OR of 2.9, 95% CI 1.4-6.0; P = 0.001), IGF2 (OR of 4.3, 95% CI 1.1-15.8; P = 0.007), CDKN2A (p16) (OR of 2.0, 95% CI 1.1-3.6; P = 0.024), and RUNX3 (OR of 3.4, 95% CI 1.3-8.7; P = 0.002) were associated with early recurrence, while MSI, CIMP, KRAS or BRAF V600E mutations were not. The CNV was significantly higher in deceased patients (CNV in 6 of 8) compared to survivors (CNV in 3 of 8). Only stage and loss of RUNX3 and CDKN2A were significant in the multivariable risk-model for early recurrence.</p>
<p>Conclusions: A high copy number variation phenotype is a strong predictor of early recurrence and death, and may indicate a dose-dependent relationship between genetic instability and outcome. Loss of tumor suppressors RUNX3 and CDKN2A were related to recurrence-risk and warrants further investigation.</p>
2015-04-16T00:00:00ZPsychiatric disorders in children with cerebral palsy. Is there a need for mental health screening?http://hdl.handle.net/1956/11041
Psychiatric disorders in children with cerebral palsy. Is there a need for mental health screening?
Bjørgaas, Hanne Marit
Doctoral thesis
<p>Cerebral palsy (CP) is one of the most prevalent neuro-motor disorders in childhood.
Previous studies using mental health questionnaires, had found mental health
problems in up to every second child with CP. Peer problems were among the most
common, often co-existing with other mental health problems. Whether a high
prevalence of mental health problems found when using screening questionnaires
reflected a high prevalence of psychiatric disorders when using stringent diagnostic
criteria, was unknown. Neither was the impact of co-existing medical conditions on
the prevalence of psychiatric disorders known, nor the feasibility of using screening
questionnaires to identify psychiatric disorders in children with CP.</p>
<p>The aims of the present thesis were to ascertain the prevalence of psychiatric
disorders in children with CP, and to assess to what extent psychiatric disorders were
associated with co-existing medical conditions. Further, the aim was to assess the
prevalence of autism spectrum symptoms in children with CP, using the Autism
Spectrum Screening Questionnaire (ASSQ). Likewise, we aimed to compare mental
health problems in children with CP to a population based sample using the Strengths
and Difficulties Questionnaire (SDQ), and to evaluate the SDQ as a screeing instrument in children with CP.</p>
<p>The thesis is based on a population including children with CP diagnosed according
to ICD-10 criteria under G.80.0-G80.9, born in 2001-2003 and living in the Western
Health Region of Norway. Children were assessed at school starting age, and parents
of all children taking part in the study were interviewed using the child psychiatric
diagnostic instrument, the Kiddie-SADS. Psychiatric disorders were diagnosed
according to DSM-IV criteria. Mental health problems were assessed using the SDQ,
and problems with social functioning were assessed using the ASSQ. Medical
information was gathered through medical records and a medical examination.</p>
<p>Psychiatric disorders were found in almost one in two children with CP according to
Kiddie-SADS. The burden of mental health problems was even higher, with two in
three children scoring above a population cut-off at 90th percentile when using the
SDQ. Peer problems were most common, with nine in ten children scoring above the
90th percentile. When using the ASSQ, one in five children scored above a population
cut-off at 98th percentile. There was a considerable co-occurrence of mental health
problems. Using the Kiddie-SADS as a gold standard, results from SDQ total
difficulties score in children with CP were compared. Sensitivity was 0.85, and
specificity was 0.55.</p>
<p>Conclusion: A high prevalence of psychiatric disorders in children with CP was
found. Autism spectrum symptoms, possibly representing autism spectrum disorders,
were highly prevalent. Co-existing medical conditions and co-occurring mental health
problems were common, representing a challenge when diagnosing psychiatric
disorders in children with CP. Mental health screening is recommended at school
starting age in children with CP.</p>
2015-06-12T00:00:00ZMental Health in Children with Cerebral Palsy: Does Screening Capture the Complexity?http://hdl.handle.net/1956/11040
Mental Health in Children with Cerebral Palsy: Does Screening Capture the Complexity?
Bjørgaas, Hanne Marit; Elgen, Irene Bircow; Bøe, Tormod; Hysing, Mari
Journal article
<p>Introduction: Children with cerebral palsy (CP), one of the most common childhood neurological disorders, often have associated
medical and psychological symptoms.This study assesses mental health problems compared to population controls and the ability
of a mental health screening tool to predict psychiatric disorders and to capture the complexity of coexisting symptoms.</p>
<p>Methods:
Children with CP (𝑁 = 47) were assessed according to DSM-IV criteria using a psychiatric diagnostic instrument (Kiddie-SADS)
and a mental health screening questionnaire (SDQ). Participants from the Bergen Child Study, a large epidemiological study,
served as controls.</p>
<p>Results: Children with CP had significantly higher means on all problem scores including impact scores. Two
in three children scored above 90th percentile cutoff on Total Difficulties Score (TDS), and 57% met criteria for a psychiatric
disorder, yielding a sensitivity of 0.85 and a specificity of 0.55. Mental health problems coexisted across symptom scales, and peer
problems were highly prevalent in all groups of psychiatric disorders.</p>
<p>Conclusion: A high prevalence of mental health problems
and cooccurrence of symptoms were found in children with CP compared to controls. Screening with SDQ detects mental health
problems, but does not predict specific disorders in children with CP.ADHDis common, but difficult to diagnose due to complexity
of symptoms. Mental health services integrated in regular followup of children with CP are recommended due to high prevalence
and considerable overlap of mental health symptoms.<p>
2013-01-01T00:00:00ZTime trends in the incidence and prevalence of multiple sclerosis in Norway during eight decadeshttp://hdl.handle.net/1956/11026
Time trends in the incidence and prevalence of multiple sclerosis in Norway during eight decades
Grytten, Nina; Torkildsen, Øivind; Myhr, Kjell-Morten
Journal article
Norway has been subjected to numerous epidemiological investigations on the prevalence and incidence of multiple sclerosis (MS), dating back to 1935. The objective of this study was to review the studies on the prevalence and incidence of MS in Norway, provide an update on the prevalence of MS in Norway, and describe the time trends in the prevalence and incidence of MS in relation to risk factors, case ascertainment, and data. We performed a systematic search on PubMed and MEDLINE up to November 2014 using the search string ‘multiple sclerosis prevalence in Norway’ or ‘multiple sclerosis incidence in Norway’. In addition, we scrutinized the reference lists of the publications identified for relevant citations. We retrieved data on the distribution of MS in Norway on December 31, 2013 from the Norwegian Multiple Sclerosis Registry and Biobank and the Norwegian Patient Registry. We identified 29 articles. From 1961 to 2014, the reported prevalence of MS increased from 20 to 203 per 100,000 inhabitants, and the incidence increased from 1.9 to 8.0 per 100,000. The nationwide crude prevalence in Norway, based on the Norwegian Patient Registry, was 208 per 100,000 on December 31, 2013. The reported prevalence of MS in Norway has increased 10-fold, with several possible causes. During eight decades, neurological health services have generally become more accessible to the population, and transforming diagnostic criteria has made the diagnosis of MS more precise and valid. There have also been changes in lifestyle behavior and known risk factors, such as vitamin D and smoking, that might have contributed to the increased incidence of MS. A possible role of increased survival in MS needs to be examined further.
2015-06-05T00:00:00ZUltrasound echo-intensity predicts severe Pancreatic affection in cystic fibrosis patientshttp://hdl.handle.net/1956/11022
Ultrasound echo-intensity predicts severe Pancreatic affection in cystic fibrosis patients
Engjom, Trond; Erchinger, Friedemann Georg; Lærum, Birger Norderud; Tjora, Erling; Gilja, Odd Helge; Dimcevski, Georg Gjorgji
Journal article
<p>Background: Pancreatic destruction affects the majority of patients with cystic fibrosis. We aimed to relate ultrasound findings to exocrine pancreatic function and cystic fibrosis genotype.</p>
<p>Methods: Patients with cystic fibrosis and a matched group of healthy controls were included. We performed transabdominal ultrasound, and recorded echo intensities of the pancreas and parenchymal characteristics according to endoscopic ultrasound based Rosemont criteria.</p>
<p>Results: We included 39 patients and 29 healthy controls. The cystic fibrosis patients were grouped according to exocrine pancreatic function; Cystic fibrosis, insufficient (n = 20) and sufficient (n = 19). Echo intensity measures and visual score demonstrated hyper-echogenicity in the pancreas insufficient group compared to the pancreas sufficient groups (p&lt;0.001). Ductal and parenchymal changes were not prevalent in any of the groups.</p>
<p>Conclusion: The hyper-echoic pancreas was the most frequent ultrasonographic finding in exocrine pancreas insufficient cystic fibrosis patients. Pancreatic echo levels correlated to pancreatic phenotype.</p>
2015-03-24T00:00:00ZAddition of eGFR and age improves the prognostic absolute renal risk-model in 1,134 norwegian patients with IgA nephropathyhttp://hdl.handle.net/1956/11021
Addition of eGFR and age improves the prognostic absolute renal risk-model in 1,134 norwegian patients with IgA nephropathy
Knoop, Thomas; Vågane, Ann Merethe; Vikse, Bjørn Egil; Svarstad, Einar; Magnusdottir, Bergrun Tinna; Leh, Sabine Maria; Reisæter, Anna Varberg; Bjørneklett, Rune
Journal article
Background: Predicting outcome in individual patients with IgA nephropathy (IgAN) is difficult but important. For this purpose, the absolute renal risk (ARR) model has been developed in a French cohort to calculate the risk of end-stage renal disease (ESRD) and death. ARR (0-3) is scored in individual IgAN patients based on the presence of proteinuria ≥1 g/24 h, hypertension, and severe histopathological lesions (1 point per risk factor). We have validated the ARR model in a Norwegian cohort of IgAN patients and tested whether adding data on initial estimated glomerular filtration rate (eGFR) and age improved prediction. Methods: IgAN patients diagnosed between 1988 and 2012 were identified in the Norwegian Kidney Biopsy Registry, and endpoints were identified by record linkage with the Norwegian Renal Registry (ESRD) and the Population Registry (deaths). Results: We identified 1,134 IgAN patients. The mean duration of follow-up was 10.2 years (range 0.0 to 25.7 years). Two hundred and fifty one patients developed ESRD and there were 69 pre-ESRD deaths. The ARR model significantly stratified the IgAN cohort according to risk of ESRD/death. The inclusion of eGFR and age significantly improved the ARR prognostic model; in the receiver operator characteristics (ROC) analysis, area under the curve (AUC) at 10-years of follow-up increased from 0.79 to 0.89, p < 0.001. Conclusions: ARR is a suitable prognostic model for stratifying IgAN patients according to the risk of ESRD or death. Including initial eGFR and age in the model substantially improved its accuracy in our nationwide cohort.
2015-05-01T00:00:00ZIntroduction of positron emission tomography into the Western Norwegian Health Region: Regional balance in resource utilization from 2009 to 2014http://hdl.handle.net/1956/11016
Introduction of positron emission tomography into the Western Norwegian Health Region: Regional balance in resource utilization from 2009 to 2014
Stokmo, Henning Langen; Reitan, Bernt Christian; Johnsen, Boel; Gulati, Ankush; Kleven-Madsen, Nina; Adamsen, Tom Christian Holm; Biermann, Martin
Journal article
<p>Background: The aim was to compare resource utilization across the four health trusts within the Western Norway Regional Health Authority since the establishment of positron emission tomography (PET) at Haukeland University Hospital in Bergen in 2009.</p>
<p>Methods: Metadata from all PET examinations from 2009 to 2014 were automatically imported from the PET centre&#39;s central production database into a custom-developed database system, MDCake. A PET examination was defined as a procedure based on a single injection of radioactive tracer. The patients&#39; place of residence and tentative diagnosis were coded based on the available clinical information.</p>
<p>Results: The total number of PET examinations increased from 293 in 2009 to 1616 in 2014. The number of PET examinations per year increased across all diagnostic groups, but plateaued for lung cancer, gastrointestinal cancer and malignant melanoma since 2013. The number of examinations per capita was evenly distributed between the three northern health trusts with an average of 1260 PET studies per million inhabitants in 2014. However, patients residing in the most southerly health trust received between 44% (2010) and 27% (2014; P&lt;0&middot;001, repeated measures ANOVA) fewer examinations per capita per year.</p>
<p>Conclusion: Centralized PET in the Western Norwegian health region meets the current clinical demand for patients residing in the three northern health trusts while patients from the most southern health trust receive approximately 30% fewer PET examinations. Access to specialized health care should be monitored routinely in order to identify inequalities in referral patterns and resource utilization.</p>
2015-01-01T00:00:00ZIs infertility really associated with higher levels of mental distress in the female population? Results from the North-Trondelag Health Study and the Medical Birth Registry of Norwayhttp://hdl.handle.net/1956/11003
Is infertility really associated with higher levels of mental distress in the female population? Results from the North-Trondelag Health Study and the Medical Birth Registry of Norway
Biringer, Eva Aaker; Howard, Louise Michele; Kessler, Ute; Stewart, Robert; Mykletun, Arnstein
Journal article
<p>Objective: To explore the effect of ever having tried to conceive for more than 12 months on levels of anxiety and depressive symptoms and to investigate if symptom levels of anxiety and depression in infertile women who remain childless, or go on to have children, respectively, differ from symptom levels in mothers without reports of infertility.</p>
<p>Methods: Analyses were based on information from 12&thinsp;584 Norwegian women aged 19&ndash;45 years who participated in the North-Tr&oslash;ndelag Health Study from 1995 to 1997 and data from the Medical Birth Registry of Norway. Anxiety and depressive symptoms were measured by the Hospital Anxiety and Depression Scale.</p>
<p>Results: Having tried to conceive for more than 12 months (ever) was weakly associated with higher levels of depressive symptoms. In the categorical analyses, women with resolved infertility had higher levels of anxiety symptoms (B&thinsp;=&thinsp;0.25 (95% confidence interval (CI)&thinsp;=&thinsp;0.04&ndash;0.47)) and voluntarily childfree had lower levels of depressive symptoms (B&thinsp;=&thinsp;&ndash;0.05 (95% CI&thinsp;=&thinsp;&ndash;0.50 to &ndash;0.21)) than mothers without infertility. However, women with current primary or current secondary infertility had levels of anxiety and depression not significantly different from mothers without infertility.</p>
<p>Conclusion: At the population level, and from a longitudinal perspective, unresolved infertility is less burdensome than findings from studies on women seeking help for infertility would suggest.</p>
2015-01-01T00:00:00ZHealth-related Quality of Life, Distress and Psychosocial Factors in Head and Neck and Renal Cancer Patients. Quality of Life in HNSCC and RCC patientshttp://hdl.handle.net/1956/11001
Health-related Quality of Life, Distress and Psychosocial Factors in Head and Neck and Renal Cancer Patients. Quality of Life in HNSCC and RCC patients
Beisland, Elisabeth
Doctoral thesis
<p>Cancer represents a major health challenge worldwide, and affects a substantial
proportion of the human population. Studies of cancer treatment has traditionally
assessed endpoints such as overall survival and progression free survival. In order to
better understand and evaluate the overall impact of the disease and its treatment,
researchers eventually also included evaluation of health related quality of life
(HRQoL) after cancer treatment. Knowledge of patient’s HRQoL and what affects
cancer patients' psychological adaptation to treatment and survival has become
increasingly important considering the growing number of cancer patients who
survive.</p>
<p>In this thesis, we have studied the relationship between HRQoL and psychosocial
factors such as personality, choice of coping, and distress (GHQ) in patients treated for
Head and Neck Squamous Cell Carcinoma (HNSCC). Except for distress, we have
studied the same factors in patients treated for Renal Cell Carcinoma (RCC). We have
also examined the importance of comorbidity, some aspects of cancer biology and
other treatment-related factors.</p>
<p>HNSCC and RCC occurs about equally as frequently in Norway. The two cancer
diagnosis groups have an approximately equal risk of recurrence and death. The big
difference between the two patient groups is according to the conditions of treatment.
HNSCC patients often receive an extensive treatment consisting of radiation therapy,
chemotherapy and surgery, which may lead to sequelae of a potentially great impact
on daily functioning. RCC patients are normally treated with one surgical procedure
only. The groups are therefore interesting to compare in terms of what determines the
perceived HRQoL. Is it the cancer prevalence, treatment related factors, risk of recurrence and death, sequelae -or other more personality-related qualities that are
decisive.</p>
<p>In HNSCC patients, we found that presence of the personality trait neuroticism and use
of avoidance- coping, were both associated with and predicts increased distress with
much the same pattern as for HRQoL. Furthermore we suggested that distress may
possibly be regarded a HRQoL variable in HNSCC patients.</p>
<p>The personality trait of neuroticism showed up to 30% common variance with
HRQoL. Large extent of primary tumor (T- stage), predicted increased distress in
HNSCC patients. Utilized coping strategy was also important, partly as mediator
between personality and HRQoL, and associated to HRQoL. Distress was found to be
stable when measured over a four-year follow-up period in the HNSCC patient
group.In our sample of RCC patients we made similar findings. Almost all HRQoLindices
were significantly negatively correlated with the personality trait neuroticism
and to use of avoidance- coping. RCC patients treated with a flank incision and to
some extent with open abdomen approach, reported impaired HRQoL in several
indexes, while those treated with minimal- invasive surgery, reported HRQoL in line
with the general population. In some areas, the flank treated RCC patients reported a
decreased HRQoL compared to a group of laryngectomized HNSCC patients.
Considering the patients HRQoL, selection of surgical access in nephron- sparing
surgery (NSS) should be viewed in the light of this finding. Comorbidity and
particularly whether the patient had diabetes or were on lung medication or not, seems
to be associated with impaired HRQoL in patients surgically treated for RCC.</p>
<p>The “European Organization for Research and Treatment of Cancer” (EORTC) has
developed several general and disease-specific quality of life questionnaires for cancer
patients, but a disease-specific questionnaire for RCC patients have so far been
lacking. We have therefore developed an EORTC-compatible RCC-specific quality of life questionnaire. Our proposed form adds important disease-specific information
about RCC- patients' HRQoL. By adding four general questions about pain, mobility
and social functioning, our form also has the potential as a stand- alone HRQoL
questionnaire that can be clinically used among surgically treated RCC patients.</p>
<p>Surprisingly similar patterns of self-reported HRQoL and distress (only in head/neck
cancer patients) on the one hand, and personality and coping on the other side,
between the head/neck and renal cancer patients were found in this study. For both
groups, it appears that the relationship between psychosocial factors and HRQOL is
three to four times as strong as the correlation between sequelae of treatment and
reported HRQOL. Comorbidity was associated with lower self-reported HRQoL.</p>
2015-12-11T00:00:00ZPost-PET ultrasound improves specificity of 18F-FDG-PET for recurrent differentiated thyroid cancer while maintaining sensitivityhttp://hdl.handle.net/1956/10985
Post-PET ultrasound improves specificity of 18F-FDG-PET for recurrent differentiated thyroid cancer while maintaining sensitivity
Biermann, Martin; Kråkenes, Jostein; Brauckhoff, Katrin; Haugland, Hans Kristian; Akslen, Lars A.; Heinecke, A.; Varhaug, Jan Erik; Brauckhoff, Michael
Journal article
Background: Positron emission tomography (PET) using fluor-18-deoxyglucose (18F-FDG) with or without computed tomography (CT) is generally accepted as the most sensitive imaging modality for diagnosing recurrent differentiated thyroid cancer (DTC) in patients with negative whole body scintigraphy with iodine-131 (I-131).
Purpose: To assess the potential incremental value of ultrasound (US) over 18F-FDG-PET-CT.
Material and Methods Fifty-one consecutive patients with suspected recurrent DTC were prospectively evaluated using the following multimodal imaging protocol: (i) US before PET (pre-US) with or without fine needle biopsy (FNB) of suspicious lesions; (ii) single photon emission computed tomography (≥3 GBq I-131) with co-registered CT (SPECT-CT); (iii) 18F-FDG-PET with co-registered contrast-enhanced CT of the neck; (iv) US in correlation with the other imaging modalities (post-US). Postoperative histology, FNB, and long-term follow-up (median, 2.8 years) were taken as composite gold standard.
Results: Fifty-eight malignant lesions were identified in 34 patients. Forty lesions were located in the neck or upper mediastinum. On receiver operating characteristics (ROC) analysis, 18F-FDG-PET had a limited lesion-based specificity of 59% at a set sensitivity of 90%. Pre-US had poor sensitivity and specificity of 52% and 53%, respectively, increasing to 85% and 94% on post-US, with knowledge of the PET/CT findings (P < 0.05 vs. PET and pre-US). Multimodal imaging changed therapy in 15 out of 51 patients (30%).
Conclusion In patients with suspected recurrent DTC, supplemental targeted US in addition to 18F-FDG-PET-CT increases specificity while maintainin sensitivity, as non-malignant FDG uptake in cervical lesions can be confirmed.
2015-03-13T00:00:00ZImproved prognosis in Norwegian patients with glomerulonephritis associated with anti-neutrophil cytoplasmic antibodieshttp://hdl.handle.net/1956/10969
Improved prognosis in Norwegian patients with glomerulonephritis associated with anti-neutrophil cytoplasmic antibodies
Sriskandarajah, Sanjeevan; Aasarød, Knut; Skrede, Steinar; Knoop, Thomas; Reisæter, Anna Varberg; Bjørneklett, Rune
Journal article
Background. Glomerulonephritis associated with anti-neutrophil cytoplasmic antibodies (ANCA) is associated with increased mortality and a high risk of end-stage renal disease (ESRD). Here, we investigated whether the prognosis has improved over the last 25 years.
Methods: Patients were identified in the Norwegian Kidney Biopsy Registry. We included all patients with pauci-immune crescentic glomerulonephritis and a positive ANCA test from 1988 to 2012. Deaths and ESRD in the cohort were identified through record linkage with the Norwegian Population Registry (deaths) and the Norwegian Renal Registry (ESRD). Outcomes of patients diagnosed in 1988–2002 were compared with outcomes of patients diagnosed in 2003–12.
Results: A cohort of 455 patients with ANCA-associated glomerulonephritis was identified. The mean follow-up was 6.0 years (range, 0.0–23.4). During the study period, 165 (36%) patients died and 124 (27%) progressed to ESRD. Compared with patients diagnosed in 1988–2002, those diagnosed in 2003–12 had higher mean initial estimated glomerular filtration rates (37 versus 27 mL/min/1.73 m2) and lower risk of ESRD (1-year risk: 13 versus 19%; 10-year risk: 26 versus 37%). The composite endpoint, ESRD or death within 0–1 year after diagnosis, was reduced from 34 to 25%. In patients over 60 years old, 1-year mortality fell from 33 to 20%.
Conclusions: In Norwegian patients with ANCA-associated glomerulonephritis, prognosis was significantly better in 2003–12 compared with 1988–2002. This improvement was probably partly due to a shorter diagnostic delay, and better therapeutic management in older patients.
2014-02-17T00:00:00ZPreoperative tumor size at MRI predicts deep myometrial invasion, lymph node metastases, and patient outcome in endometrial carcinomashttp://hdl.handle.net/1956/10957
Preoperative tumor size at MRI predicts deep myometrial invasion, lymph node metastases, and patient outcome in endometrial carcinomas
Ytre-Hauge, Sigmund; Husby, Jenny Hild Aase; Magnussen, Inger Johanne; Werner, Henrica Maria Johanna; Salvesen, Øyvind; Bjørge, Line; Trovik, Jone; Stefansson, Ingunn; Salvesen, Helga Birgitte; Haldorsen, Ingfrid S.
Journal article
OBJECTIVE: The aim of this study was to explore the relation between preoperative tumor size based on magnetic resonance imaging (MRI) and the surgical pathologic staging parameters (deep myometrial invasion, cervical stroma invasion, and metastatic lymph nodes) and to assess the prognostic impact of tumor size in endometrial carcinomas. Interobserver variability for the different tumor size measurements was also assessed.
METHODS/MATERIALS: Preoperative pelvic MRI of 212 patients with histologically confirmed endometrial carcinomas was read independently by 3 radiologists. Maximum tumor diameters were measured in 3 orthogonal planes (anteroposterior, transverse, and craniocaudal planes [CC]), and tumor volumes were estimated. Tumor size was analyzed in relation to surgical staging results and patient survival. The multivariate analyses were adjusted for preoperative risk status based on endometrial biopsy. Intraclass correlation coefficients and receiver operating characteristics curves for the different tumor measurements were also calculated.
RESULTS: Anteroposterior tumor diameter independently predicted deep myometrial invasion (P < 0.001), whereas CC tumor diameter tended to independently predict lymph node metastases (P = 0.06). Based on receiver operating characteristic curves, the following tumor size cutoff values were identified: anteroposterior diameter greater than 2 cm predicted deep myometrial invasion (unadjusted odds ratio [OR], 12.4; P < 0.001; adjusted OR, 6.7; P < 0.001) and CC diameter greater than 4 cm predicted lymph node metastases (unadjusted OR, 6.2; P < 0.001; adjusted OR, 4.9; P = 0.009). Large tumor size was associated with reduced progression/recurrence-free survival (P ≤ 0.005 for all size parameters), and CC diameter had an independent impact on survival (adjusted hazards ratio, 1.04; P = 0.009). The interobserver variability for the different size measurements was very low (intraclass correlation coefficient, 0.78-0.85).
CONCLUSIONS: Anteroposterior tumor diameter greater than 2 cm predicts deep myometrial invasion, and CC tumor diameter greater than 4 cm predicts lymph node metastases. Tumor size is a strong prognostic factor in endometrial carcinomas. Preoperative tumor measurements based on MRI may potentially improve preoperative risk stratification models and thus enable better tailored surgical treatment in endometrial cancer.
2015-01-01T00:00:00ZMicroRNAs as important players and biomarkers in oral carcinogenesishttp://hdl.handle.net/1956/10929
MicroRNAs as important players and biomarkers in oral carcinogenesis
Min, Anjie; Zhu, Chao; Peng, Shuping; Rajthala, Saroj; Costea, Daniela Elena; Sapkota, Dipak
Journal article
Oral cancer, represented mainly by oral squamous cell carcinoma (OSCC), is the eighth most common type of human cancer worldwide. The number of new OSCC cases is increasing worldwide, especially in the low-income countries, and the prognosis remains poor in spite of recent advances in the diagnostic and therapeutic modalities. MicroRNAs (miRNAs), 18–25 nucleotides long noncoding RNA molecules, have recently gained significant attention as potential regulators and biomarkers for carcinogenesis. Recent data show that several miRNAs are deregulated in OSCC, and they have either a tumor suppressive or an oncogenic role in oral carcinogenesis. This review summarizes current knowledge on the role of miRNAs as tumor promotors or tumor suppressors in OSCC development and discusses their potential value as diagnostic and prognostic markers in OSCC.
2015-01-01T00:00:00ZComplicating autoimmune diseases in myasthenia gravis: A reviewhttp://hdl.handle.net/1956/10922
Complicating autoimmune diseases in myasthenia gravis: A review
Nacu, Aliona; Andersen, Jintana Bunpan; Lisnic, Vitalie; Owe, Jone Furulund; Gilhus, Nils Erik
Journal article
Myasthenia gravis (MG) is a rare autoimmune disease of skeletal muscle endplates. MG subgroup is relevant for comorbidity, but usually not accounted for. MG patients have an increased risk for complicating autoimmune diseases, most commonly autoimmune thyroid disease, systemic lupus erythematosus and rheumatoid arthritis. In this review, we present concomitant autoimmune disorders associated with the different MG subgroups, and show how this influences treatment and prognosis. Concomitant MG should always be considered in patients with an autoimmune disorder and developing new neuromuscular weakness, fatigue or respiratory failure. When a second autoimmune disorder is suspected, MG should be included as a differential diagnosis.
2015-04-27T00:00:00ZRefined phenotyping identifies links between preeclampsia and related diseases in a Norwegian preeclampsia family cohorthttp://hdl.handle.net/1956/10918
Refined phenotyping identifies links between preeclampsia and related diseases in a Norwegian preeclampsia family cohort
Thomsen, Liv Cecilie Vestrheim; Melton, Philip E.; Tollaksen, Kjersti; Lyslo, Ingvill; Roten, Linda Tømmerdal; Odland, Maria Lisa; Strand, Kristin Melheim; Nygård, Ottar; Sun, Chen; Iversen, Ann-Charlotte; Austgulen, Rigmor; Moses, Eric; Bjørge, Line
Journal article
Objective: Preeclampsia is a complex genetic disease of pregnancy with a heterogenous presentation, unknown cause and potential severe outcomes for both mother and child. Preeclamptic women have increased risk for atherothrombotic cardiovascular disease. We aimed to identify heritabilities and phenotypic correlations of preeclampsia and related conditions in the Norwegian Preeclampsia Family Biobank.
Methods: By applying a variance components model, a total of 493 individuals (from 138 families with increased occurrence of preeclampsia) were classified according to 30 disease-related phenotypes.
Results: Of parous women, 75.7% (263/338) had experienced preeclampsia and 35.7% of women with and 22.4% without preeclampsia delivered children small for gestational age (SGA). We identified 11 phenotypes as heritable. The increased occurrence of preeclampsia was reflected by the presence [heritability (H2r) = 0.60)] and severity (H2r = 0.15) of preeclampsia and being born in a preeclamptic pregnancy (H2r = 0.25). Other heritable phenotypes identified included SGA (H2r = 0.40), chronic hypertension (H2r = 0.57), severity of atherothrombotic cardiovascular disease (H2r = 0.31), BMI (H2r = 0.60) and pulmonary disease (H2r = 0.91). The heritable phenotype preeclampsia overlapped with SGA (P = 0.03), whereas pulmonary disease was phenotypically correlated with atherothrombotic cardiovascular disease (P < 0.01), SGA (P = 0.02) and BMI (P = 0.02).
Conclusion: This is the first study identifying the H2r of a range of health-related conditions in preeclamptic families. Our study demonstrates how refinement of phenotypes leads to better H2r estimation and the identification of a biological relationship between preeclampsia and related traits.
2015-11-01T00:00:00ZFingolimod does not enhance cerebellar remyelination in the cuprizone modelhttp://hdl.handle.net/1956/10915
Fingolimod does not enhance cerebellar remyelination in the cuprizone model
Alme, Maria Nordheim; Nystad, Agnes Elisabeth; Bø, Lars; Myhr, Kjell-Morten; Vedeler, Christian A.; Wergeland, Stig; Torkildsen, Øivind
Journal article
Fingolimod (FTY720) is approved for treatment of relapsing–remitting multiple sclerosis. In vitro studies have found that fingolimod stimulates remyelination in cerebellar slices, but in vivo animal studies have not detected any positive effect on cerebral remyelination. The discrepant findings could be a result of different mechanisms underlying cerebral and cerebellar remyelination. The cuprizone model for de- and remyelination was used to evaluate whether fingolimod had an impact on cerebellar remyelination in vivo. We found that fingolimod did not have any effect on cerebellar remyelination, number of mature oligodendrocytes, microglia or astrocytes when fed after cuprizone exposure.
2015-08-01T00:00:00ZF18-FDG-PET for recurrent differentiated thyroid cancer: a systematic meta-analysishttp://hdl.handle.net/1956/10865
F18-FDG-PET for recurrent differentiated thyroid cancer: a systematic meta-analysis
Haslerud, Torjan Magne; Brauckhoff, Katrin; Reisæter, Lars Anders Rokne; Lein, Regina Küfner; Heinecke, A.; Varhaug, Jan Erik; Biermann, Martin
Journal article
Background Positron emission tomography (PET) with fluor-18-deoxy-glucose (FDG) is widely used for diagnosing recurrent or metastatic disease in patients with differentiated thyroid cancer (DTC).
Purpose To assess the diagnostic accuracy of FDG-PET for DTC in patients after ablative therapy.
Material and Methods A systematic search was conducted in Medline/PubMed, EMBASE, Cochrane Library, Web of Science, and Open Grey looking for all English-language original articles on the performance of FDG-PET in series of at least 20 patients with DTC having undergone ablative therapy including total thyroidectomy. Diagnostic performance measures were pooled using Reitsma’s bivariate model.
Results Thirty-four publications between 1996 and 2014 met the inclusion criteria. Pooled sensitivity and specificity were 79.4% (95% confidence interval [CI], 73.9–84.1) and 79.4% (95% CI, 71.2–85.4), respectively, with an area under the curve of 0.858.
Conclusion F18-FDG-PET is a useful method for detecting recurrent DTC in patients having undergone ablative therapy.
2015-07-09T00:00:00ZMagnetization transfer ratio does not correlate to myelin content in the brain in the MOG-EAE mouse modelhttp://hdl.handle.net/1956/10851
Magnetization transfer ratio does not correlate to myelin content in the brain in the MOG-EAE mouse model
Fjær, Sveinung; Bø, Lars; Myhr, Kjell-Morten; Torkildsen, Øivind; Wergeland, Stig
Journal article
Magnetization transfer ratio (MTR) is a magnetic resonance imaging (MRI) method which may detect
demyelination not detected by conventional MRI in the central nervous system of patients with multiple
sclerosis (MS). A decrease in MTR value has previously been shown to correlate to myelin loss in the
mouse cuprizone model for demyelination. In this study, we investigated the sensitivity of MTR for demyelination in the myelin oligodendrocyte (MOG) 1–125 induced experimental autoimmune
encephalomyelitis (EAE) mouse model. A total of 24 female c57Bl/6 mice were randomized to a control
group (N = 6) or EAE (N = 18). MTR images were obtained at a preclinical 7 Tesla Bruker MR-scanner before EAE induction (baseline), 17–19 days (midpoint) and 31–32 days (endpoint) after EAE induction. Mean MTR values were calculated in five regions of the brain and compared to weight, EAE severity score and myelin content assessed by immunostaining for proteolipid protein and luxol fast blue, lymphocyte and monocyte infiltration and iron deposition. Contrary to what was expected, MTR values in the EAE mice were higher than in the control mice at the midpoint and endpoint. No significant difference in myelin content was found according to histo- or immunohistochemistry. Changes in MTR values did not correlate to myelin content, iron content, lymphocyte or monocyte infiltration, weight or EAE severity scores. This suggest that MTR measures of brain tissue can give significant differences between control mice and EAE mice not caused by demyelination, inflammation or iron deposition, and may not be useful surrogate markers for demyelination in the MOG1-125 mouse model.
2015-03-02T00:00:00ZRisk factors, complications and survival after upper abdominal surgery: A prospective cohort studyhttp://hdl.handle.net/1956/10845
Risk factors, complications and survival after upper abdominal surgery: A prospective cohort study
Aahlin, Eirik Kjus; Tranø, Geir; Johns, Neil; Horn, Arild; Søreide, Jon Arne; Fearon, Kenneth Christopher H.; Revhaug, Arthur; Lassen, Kristoffer
Journal article
<p>Background: Preoperative weight loss and abnormal serum-albumin have traditionally been associated with reduced survival. More recently, a correlation between postoperative complications and reduced long-term survival has been reported and the significance of the relative proportion of skeletal muscle, visceral and subcutaneous adipose tissue has been examined with conflicting results. We investigated how preoperative body composition and major non-fatal complications related to overall survival and compared this to established predictors in a large cohort undergoing upper abdominal surgery.</p>
<p>Methods: From 2001 to 2006, 447 patients were included in a Norwegian multicenter randomized controlled trial in major upper abdominal surgery. Patients were now, six years later, analyzed as a single prospective cohort and overall survival was retrieved from the National Population Registry. Body composition indices were calculated from CT images taken within three months preoperatively.</p>
<p>Results: Preoperative serum-albumin &lt;35 g/l (HR = 1.52, p = 0 .014) and weight loss &gt;5 % (HR = 1.38, p = 0.023) were independently associated with reduced survival. There was no association between any of the preoperative body composition indices and reduced survival. Major postoperative complications were independently associated with reduced survival but only as long as patients who died within 90 days were included in the analysis.</p>
<p>Conclusions: Our study has confirmed the robust significance of the traditional indicators, preoperative serum-albumin and weight loss. The body composition indices did not prove beneficial as global indicators of poor prognosis in upper abdominal surgery. We found no association between non-fatal postoperative complications and long-term survival.</p>
2015-07-07T00:00:00ZEthical challenges in nursing homes - staff's opinions and experiences with systematic ethics meetings with participation of residents' relatives.http://hdl.handle.net/1956/10816
Ethical challenges in nursing homes - staff's opinions and experiences with systematic ethics meetings with participation of residents' relatives.
Bollig, Georg; Schmidt, Gerda; Rosland, Jan Henrik; Heller, Andreas
Journal article
Background
Many ethical problems exist in nursing homes. These include, for example, decision-making in end-of-life care, use of restraints and a lack of resources.
Aims
The aim of the present study was to investigate nursing home staffs’ opinions and experiences with ethical challenges and to find out which types of ethical challenges and dilemmas occur and are being discussed in nursing homes.
Methods
The study used a two-tiered approach, using a questionnaire on ethical challenges and systematic ethics work, given to all employees of a Norwegian nursing home including nonmedical personnel, and a registration of systematic ethics discussions from an Austrian model of good clinical practice.
Results
Ninety-one per cent of the nursing home staff described ethical problems as a burden. Ninety per cent experienced ethical problems in their daily work. The top three ethical challenges reported by the nursing home staff were as follows: lack of resources (79%), end-of-life issues (39%) and coercion (33%). To improve systematic ethics work, most employees suggested ethics education (86%) and time for ethics discussion (82%). Of 33 documented ethics meetings from Austria during a 1-year period, 29 were prospective resident ethics meetings where decisions for a resident had to be made. Agreement about a solution was reached in all 29 cases, and this consensus was put into practice in all cases. Residents did not participate in the meetings, while relatives participated in a majority of case discussions. In many cases, the main topic was end-of-life care and life-prolonging treatment.
Conclusions
Lack of resources, end-of-life issues and coercion were ethical challenges most often reported by nursing home staff. The staff would appreciate systematic ethics work to aid decision-making. Resident ethics meetings can help to reach consensus in decision-making for nursing home patients. In the future, residents’ participation should be encouraged whenever possible.
2015-04-28T00:00:00ZEffects of ECT in treatment of depression: Study protocol for a prospective neuroradiological study of acute and longitudinal effects on brain structure and functionhttp://hdl.handle.net/1956/10793
Effects of ECT in treatment of depression: Study protocol for a prospective neuroradiological study of acute and longitudinal effects on brain structure and function
Oltedal, Leif; Kessler, Ute; Ersland, Lars; Grüner, Renate; Andreassen, Ole Andreas; Haavik, Jan; Hoff, Per Ivar; Hammar, Åsa; Dale, Anders Martin; Hugdahl, Kenneth; Ødegaard, Ketil Joachim
Journal article
Background
Major depression can be a serious and debilitating condition. For some patients in a treatment resistant depressive episode, electroconvulsive treatment (ECT) is the only treatment that is effective. Although ECT has shown efficacy in randomized controlled trials, the treatment is still controversial and stigmatized. This can in part be attributed to our lack of knowledge of the mechanisms of action. Some reports also suggest potential harmful effects of ECT treatment and memory related side effects have been documented.
Methods/design
The present study will apply state of the art radiology through advanced magnetic resonance imaging (MRI) techniques to investigate structural and functional brain effects of ECT. As a multi-disciplinary collaboration, imaging findings will be correlated to psychiatric response parameters, neuropsychological functioning as well as neurochemical and genetic biomarkers that can elucidate the underlying mechanisms. The aim is to document both treatment effects and potential harmful effects of ECT.
Sample: n = 40 patients in a major depressive episode (bipolar and major depressive disorder). Two control groups with n = 15 in each group: age and gender matched healthy volunteers not receiving ECT and patients undergoing electrical cardioversion (ECV) for atrial fibrillation (AF). Observation time: six months.
Discussion
The study will contribute to our understanding of the pathophysiology of major depression as well as mechanisms of action for the most effective treatment for the disorder; ECT.
2015-05-01T00:00:00ZThe study protocol of the Norwegian randomized controlled trial of electroconvulsive therapy in treatment resistant depression in bipolar disorderhttp://hdl.handle.net/1956/10754
The study protocol of the Norwegian randomized controlled trial of electroconvulsive therapy in treatment resistant depression in bipolar disorder
Kessler, Ute; Vaaler, Arne E.; Schøyen, Helle; Ødegaard, Ketil Joachim; Bergsholm, Per; Andreassen, Ole Andreas; Malt, Ulrik Fredrik; Morken, Gunnar
Journal article
Background
The treatment of depressive phases of bipolar disorder is challenging. The effects of the commonly used antidepressants in bipolar depression are questionable. Electroconvulsive therapy is generally considered to be the most effective treatment even if there are no randomized controlled trials of electroconvulsive therapy in bipolar depression. The safety of electroconvulsive therapy is well documented, but there are some controversies as to the cognitive side effects. The aim of this study is to compare the effects and side effects of electroconvulsive therapy to pharmacological treatment in treatment resistant bipolar depression. Cognitive changes and quality of life during the treatment will be assessed.
Methods/Design
A prospective, randomised controlled, multi-centre six- week acute treatment trial with seven clinical assessments. Follow up visit at 26 weeks or until remission (max 52 weeks). A neuropsychological test battery designed to be sensitive to changes in cognitive function will be used. Setting: Nine study centres across Norway, all acute psychiatric departments. Sample: n = 132 patients, aged 18 and over, who fulfil criteria for treatment resistant depression in bipolar disorder, Montgomery Åsberg Depression Rating Scale Score of at least 25 at baseline. Intervention: Intervention group: 3 sessions per week for up to 6 weeks, total up to 18 sessions. Control group: algorithm-based pharmacological treatment as usual.
Discussion
This study is the first randomized controlled trial that aims to investigate whether electroconvulsive therapy is better than pharmacological treatment as usual in treatment resistant bipolar depression. Possible long lasting cognitive side effects will be evaluated. The study is investigator initiated, without support from industry.
2010-02-23T00:00:00ZRecommendations for initiation and cessation of enzyme replacement therapy in patients with Fabry disease: the European Fabry Working Group consensus documenthttp://hdl.handle.net/1956/10751
Recommendations for initiation and cessation of enzyme replacement therapy in patients with Fabry disease: the European Fabry Working Group consensus document
Biegstraaten, Marieke; Arngrímsson, R; Barbey, F; Boks, L; Cecchi, Franco; Deegan, PB; Feldt-Rasmussen, Ulla; Geberhiwot, T; Germain, DP; Hendriksz, C; Hughes, DA; Kantola, I; Karabul, N; Lavery, C; Linthorst, GE; Mehta, A; van de Mheen, E; Oliveira, JP; Parini, R; Ramaswami, Uma; Rudnicki, M; Serra, A; Sommer, Claudia; Sunder-Plassmann, G; Svarstad, Einar; Sweeb, A; Terryn, W; Tylki-Szymanska, A; Tøndel, Camilla; Vujkovac, B; Weidemann, Frank; Wijburg, FA; Woolfson, P; Hollak, CE.
Journal article
Introduction
Fabry disease (FD) is a lysosomal storage disorder resulting in progressive nervous system, kidney and heart disease. Enzyme replacement therapy (ERT) may halt or attenuate disease progression. Since administration is burdensome and expensive, appropriate use is mandatory. We aimed to define European consensus recommendations for the initiation and cessation of ERT in patients with FD.
Methods
A Delphi procedure was conducted with an online survey (n = 28) and a meeting (n = 15). Patient organization representatives were present at the meeting to give their views. Recommendations were accepted with ≥75% agreement and no disagreement.
Results
For classically affected males, consensus was achieved that ERT is recommended as soon as there are early clinical signs of kidney, heart or brain involvement, but may be considered in patients of ≥16 years in the absence of clinical signs or symptoms of organ involvement. Classically affected females and males with non-classical FD should be treated as soon as there are early clinical signs of kidney, heart or brain involvement, while treatment may be considered in females with non-classical FD with early clinical signs that are considered to be due to FD. Consensus was achieved that treatment should not be withheld from patients with severe renal insufficiency (GFR < 45 ml/min/1.73 m2) and from those on dialysis or with cognitive decline, but carefully considered on an individual basis. Stopping ERT may be considered in patients with end stage FD or other co-morbidities, leading to a life expectancy of <1 year. In those with cognitive decline of any cause, or lack of response for 1 year when the sole indication for ERT is neuropathic pain, stopping ERT may be considered. Also, in patients with end stage renal disease, without an option for renal transplantation, in combination with advanced heart failure (NYHA class IV), cessation of ERT should be considered. ERT in patients who are non-compliant or fail to attend regularly at visits should be stopped.
Conclusion
The recommendations can be used as a benchmark for initiation and cessation of ERT, although final decisions should be made on an individual basis. Future collaborative efforts are needed for optimization of these recommendations.
2015-05-27T00:00:00ZAssociation of gender to outcome after out-of-hospital cardiac arrest - a report from the International Cardiac Arrest Registryhttp://hdl.handle.net/1956/10723
Association of gender to outcome after out-of-hospital cardiac arrest - a report from the International Cardiac Arrest Registry
Karlsson, Viktor; Dankiewicz, Josef; Nielsen, Niklas; Kern, Karl B.; Mooney, Michael R.; Riker, Richard R.; Rubertsson, Sten; Seder, David B.; Stammet, Pascal; Sunde, Kjetil; Søreide, Eldar; Unger, Barbara T.; Friberg, Hans
Journal article
Introduction
Previous studies have suggested an effect of gender on outcome after out-of-hospital cardiac arrest (OHCA), but the results are conflicting. We aimed to investigate the association of gender to outcome, coronary angiography (CAG) and adverse events in OHCA survivors treated with mild induced hypothermia (MIH).
Methods
We performed a retrospective analysis of prospectively collected data from the International Cardiac Arrest Registry. Adult patients with a non-traumatic OHCA and treated with MIH were included. Good neurological outcome was defined as a cerebral performance category (CPC) of 1 or 2.
Results
A total of 1,667 patients, 472 women (28%) and 1,195 men (72%), met the inclusion criteria. Men were more likely to receive bystander cardiopulmonary resuscitation, have an initial shockable rhythm and to have a presumed cardiac cause of arrest. At hospital discharge, men had a higher survival rate (52% vs. 38%, P <0.001) and more often a good neurological outcome (43% vs. 32%, P <0.001) in the univariate analysis. When adjusting for baseline characteristics, male gender was associated with improved survival (OR 1.34, 95% CI 1.01 to 1.78) but no longer with neurological outcome (OR 1.24, 95% CI 0.92 to 1.67). Adverse events were common; women more often had hypokalemia, hypomagnesemia and bleeding requiring transfusion, while men had more pneumonia. In a subgroup analysis of patients with a presumed cardiac cause of arrest (n = 1,361), men more often had CAG performed on admission (58% vs. 50%, P = 0.02) but this discrepancy disappeared in an adjusted analysis.
Conclusions
Gender differences exist regarding cause of arrest, adverse events and outcome. Male gender was independently associated with survival but not with neurological outcome.
2015-04-21T00:00:00ZPerioperative interventions and postoperative outcomeshttp://hdl.handle.net/1956/10698
Perioperative interventions and postoperative outcomes
Jammer, Ib
Doctoral thesis
<p>Background: Postoperative complications are frequent causes of postoperative
mortality. Such complications may also lead to a prolonged period with decreased
functional and cognitive status. Perioperative care is a factor in postoperative
morbidity and mortality. Until now no common international definitions and
classifications of postoperative complications have been established.</p>
<p>The group of surgical patients with the highest risk of postoperative complications
accounts for perhaps 80% of intra-hospital deaths. With the high volume of surgery
performed worldwide, even a slight reduction in complications would result in a lower
number of preventable deaths. There are several theories on how to decrease
postoperative complications and improve patient safety and patient care. Two factors,
checklists and perioperative fluid balance, are investigated in this thesis.</p>
<p>The overall aim of this thesis is twofold:
1. To study perioperative complications and outcome after major surgery
- Paper I aimed at creating standard definitions of outcome measures for use in
pragmatic large perioperative clinical trials.
- Paper II aimed at providing data on perioperative mortality after non-cardiac
surgery across Europe.
2. To contribute in finding ways to reduce complications after major surgery
- Paper III aimed at identifying the prevalence of surgical checklist use and
possible relationship with mortality.
- Paper IV aimed at evaluating the effect of perioperative goal directed fluid
therapy guided by ScvO2 in open colorectal surgery.</p>
<p>Result: Paper I was a literature review to assess the current state of knowledge about
surgical outcome definitions. A standardized list was created for use in perioperative
research and clinical audition. The outcome measures described are organized into
four different categories: Individual adverse events, Composite outcomes, Grading of
complications and Health related quality of life.</p>
<p>Paper II was a 7 day cohort study (European Surgical Outcome Study) conducted in
498 hospitals across 28 European countries. Intra-hospital mortality data was
registered for all adult patients undergoing non-cardiac surgery. The overall intrahospital
mortality throughout Europe was 4%. A variation in mortality after surgery
throughout Europe could be confirmed. This may indicate a discrepancy in standard of
care. Identification and standardisation of key factors in perioperative care would
subsequently improve outcome throughout Europe.</p>
<p>Paper III determined the point prevalence of checklist use in Europe and its
association with in-hospital mortality, using data collected from the European Surgical
Outcome Study. There was a marked variation between checklist use and mortality in
Europe. The use of a surgical checklist was associated with lower mortality. Although
there is no causality demonstrated, checklist use may be an indicator of hospitals
focusing on improved perioperative care and therefore decrease mortality.</p>
<p>Paper IV investigated the use of goal directed fluid therapy in 241 patients
undergoing abdominal surgery and its influence on postoperative morbidity. Patients
were randomized in a control group receiving standard fluid therapy and an
intervention group using central venous oxygen saturation as a surrogate for cardiac
output to guide fluid therapy. Although there was a difference in the amount of fluid
given between the two groups, the complication rate 30 days after surgery was equal.</p>
<p>Conclusion: We proposed standardised outcome measures for use in future trials
investigating postoperative complications. This contributes to a meaningful
comparison of quality of care in future clinical trials and leaves less room for
interpretation of outcome measures. It is not likely that one single intervention in the
perioperative period will markedly affect outcome. Most likely a multifactorial
intervention will be successful in reaching this goal. However, specific research in the
high-risk surgical population is lacking. It can be assumed that this patient group
would have the greatest benefit from an improved perioperative care pathway.
Better data may be available after foundation of national and international
perioperative registers. This may help to establish a greater research community in perioperative outcome research and assist to identify factors in the perioperative care
pathway that improve outcome.</p>
2015-11-05T00:00:00ZChanging paradigms of anterior cruciate ligament surgery. From transtibial to a more anatomic approachhttp://hdl.handle.net/1956/10677
Changing paradigms of anterior cruciate ligament surgery. From transtibial to a more anatomic approach
Inderhaug, Eivind
Doctoral thesis
<p>The current thesis consists of four papers evaluating results after anterior cruciate
ligament reconstruction using two different surgical techniques. Paper I and II
evaluate long-term outcomes after a transtibial technique using a so-called “antiimpingement”
guide for tibial tunnel placement. Clinical examination, patient
reported outcome measures and radiographic osteoarthritis/tunnel placement
evaluation was performed. Paper III and IV utilized postoperative 3D-CT to evaluate
graft tunnel placement in a cohort of patients in the midst of a change from the
transtibial technique to an AM-portal (or more anatomic) technique. Femoral tunnel
placement was measured relative to an empirical anatomic centre (based on an
average native femoral insertion from a range of anatomic studies).</p>
<p>Paper I and II found a low revision rate of 4%, good patient reported outcomes
(PROMs) – in terms of mean Lysholm score of 89 and mean IKDC subjective score
of 83 – and a low prevalence of osteoarthritis. At clinical examination, however, there
was a 20% incidence of 2+ pivot shift, indicating a significant failure in restoring
native knee kinematics. Further, a 24% incidence of posterior tibial tunnels – defined
as 50% or more along the anterior-posterior direction of the tibial plateau – was found
to be related to rotatory instability (2+ pivot shift) with associated significant worse
outcome in PROMs. Paper III and IV depicted the change in femoral tunnel position
from the transtibial technique to the AM-portal technique, with an initial great
variation in tunnel positions indicating that ACL remnants and bony landmarks were
unreliable for guiding femoral tunnel placement. Further, both the feedback from
postoperative CT assessments (Study I) and the use of intraoperative fluoroscopy
(Study II) were found to bring the femoral tunnel position closer to an empirical
femoral tunnel reference.</p>
<p>In sum, Paper I and II adds to the critique of the transtibial technique for
femoral tunnel placement and displays that avoidance of overly anterior tibial tunnel
placement (by the anti-impingement guide) can lead to a high incidence of posterior
tunnel placements. Further, the importance of a multitudinous approach for outcome evaluation is emphasized. Study III and IV shed light on one plausible reason for a
learning curve of the AM portal approach for ACL reconstruction. Using per- or
postoperative evaluation of tunnel placement can help avoid an unwanted variation in
femoral tunnels – but ultimately the results needs to be linked to finite outcome
evaluation to establish the clinical impact.</p>
2015-10-09T00:00:00ZKRAS mutation in patients undergoing hepatic resection for colorectal liver metastasis: A biomarker of cancer biology or a byproduct of patient selection?http://hdl.handle.net/1956/10583
KRAS mutation in patients undergoing hepatic resection for colorectal liver metastasis: A biomarker of cancer biology or a byproduct of patient selection?
Søreide, Kjetil; Sandvik, Odd Mathias; Søreide, Jon Arne
Journal article
2014-12-01T00:00:00ZThe ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic datahttp://hdl.handle.net/1956/10581
The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data
Christoforou, Andrea; Le Hellard, Stephanie; Giddaluru, Sudheer; Steen, Vidar Martin; The ENIGMA Consortium
Journal article
The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA’s first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
2014-06-01T00:00:00ZCountrywise results of total hip replacement. An analysis of 438,733 hips based on the Nordic Arthroplasty Register Association databasehttp://hdl.handle.net/1956/10575
Countrywise results of total hip replacement. An analysis of 438,733 hips based on the Nordic Arthroplasty Register Association database
Mäkelä, Keijo T.; Matilainen, Markus; Pulkkinen, Pekka; Fenstad, Anne Marie; Havelin, Leif Ivar; Engesæter, Lars B.; Furnes, Ove; Overgaard, Søren; Pedersen, Alma Becic; Kärrholm, Johan; Malchau, Henrik; Garellick, Göran; Ranstam, Jonas; Eskelinen, Antti
Journal article
<p>Background and purpose: An earlier Nordic Arthroplasty Register Association (NARA) report on 280,201 total hip replacements (THRs) based on data from 1995&ndash;2006, from Sweden, Norway, and Denmark, was published in 2009. The present study assessed THR survival according to country, based on the NARA database with the Finnish data included.</p>
<p>Material and methods: 438,733 THRs performed during the period 1995&ndash;2011 in Sweden, Denmark, Norway, and Finland were included. Kaplan-Meier survival analysis was used to calculate survival probabilities with 95% confidence interval (CI). Cox multiple regression, with adjustment for age, sex, and diagnosis, was used to analyze implant survival with revision for any reason as endpoint.</p>
<p>Results: The 15-year survival, with any revision as an endpoint, for all THRs was 86% (CI: 85.7&ndash;86.9) in Denmark, 88% (CI: 87.6&ndash;88.3) in Sweden, 87% (CI: 86.4&ndash;87.4) in Norway, and 84% (CI: 82.9&ndash;84.1) in Finland. Revision risk for all THRs was less in Sweden than in the 3 other countries during the first 5 years. However, revision risk for uncemented THR was less in Denmark than in Sweden during the sixth (HR = 0.53, CI: 0.34&ndash;0.82), seventh (HR = 0.60, CI: 0.37&ndash;0.97), and ninth (HR = 0.59, CI: 0.36&ndash;0.98) year of follow-up.</p>
<p>Interpretation: The differences in THR survival rates were considerable, with inferior results in Finland. Brand-level comparison of THRs in Nordic countries will be required.</p>
2014-01-01T00:00:00ZEndocrine cells in the oxyntic mucosa of the stomach in patients with irritable bowel syndromehttp://hdl.handle.net/1956/10574
Endocrine cells in the oxyntic mucosa of the stomach in patients with irritable bowel syndrome
El-Salhy, Magdy; Gilja, Odd Helge; Gundersen, Doris Irene; Hausken, Trygve
Journal article
<p>AIM: To study the different endocrine cell types in the oxyntic mucosa of patients with irritable bowel syndrome (IBS).</p>
<p>METHODS: Seventy-six patients with IBS were included in the study (62 females and 14 males; mean age 32 years, range 18-55 years), of which 40 also fulfilled the Rome III criteria for functional dyspepsia (FDP). Of the entire IBS cohort, 26 had diarrhea as the predominant symptom (IBS-D), 21 had a mixture of diarrhea and constipation (IBS-M), and 29 had constipation as the predominant symptom (IBS-C). Forty-three age and sex-matched healthy volunteers without any gastrointestinal complaints served as controls. The patients were asked to complete the Birmingham IBS symptom questionnaire. Both the patients and controls underwent a standard gastroscopy, during which three biopsy samples were taken from the corpus. Sections from these biopsy samples were immunostained using the avidin-biotin complex (ABC) method, for ghrelin, serotonin, somatostatin and histamine. The densities of these cell types and immunoreactivity intensities were quantified using computerized image analysis with Olympus cellSens imaging software (version 1.7).</p>
<p>RESULTS: The densities of the ghrelin cells in the control, IBS-total, IBS-D, IBS-M and IBS-C groups were 389 (320, 771), 359 (130, 966), 966 (529, 1154), 358 (120, 966) and 126 (0, 262) cells/mm2, respectively. There was a significant difference between the tested groups (P &lt; 0.0001). Dunn&rsquo;s multiple comparison test showed that the ghrelin cell density was significantly higher in IBS-D and lower in IBS-C than in the controls (P = 0.03 and 0.0008, respectively). The ghrelin cell density in patients with both IBS and FDP was 489 (130, 966), and in those with IBS only 490 (130, 956). There was no statistical significant difference between these 2 groups of patients (P = 0.9). The immunoreactivity intensity did not differ between any of the groups (P = 0.6). The diarrhea score of the Birmingham IBS symptom questionnaire was significantly positively correlated with ghrelin cell density (r = 0.65; P &lt; 0.0001) and significantly inversely correlated with that of constipation (r = 90.69; P &lt; 0.0001). The densities of the serotonin cells were 63 (51, 82), 51 (25, 115), 120 (69, 128), 74 (46, 123) and 40 (0, 46) cells/mm2 in the control, IBS-total, IBS-D, IBS-M and IBS-C groups, respectively. A statistically significant difference was found between the tested groups (P &lt; 0.0001). Posttest revealed that serotonin cell density was significantly higher in IBS-D and lower in IBS-C than in controls (P = 0.02 and 0.004, respectively), but did not differ in the IBS-total and IBS-M groups from that in controls (P = 0.5 and 0.4, respectively). The serotonin cell density in patients with both IBS and FDP was 62 (25, 115) and in those with IBS only 65 (25, 123). There was no statistically significant difference between these 2 groups of patients (P = 1). The immunoreactivity intensity of serotonin did not differ significantly between any of the groups (P = 0.0.9). The serotonin cell density was significantly positively correlated with the diarrhea score of the Birmingham IBS symptom questionnaire (r = 0.56; P &lt; 0.0001) and significantly inversely correlated with that of constipation (r = 0.51; P &lt; 0.0001). The densities of the somatostatin cells were 97 (72, 126), 72 (0, 206), 29 (0, 80), 46 (0, 103) and 206 (194, 314) cells/mm2 in the control, IBS-total, IBS-D, IBS-M and IBS-C groups, respectively (Figures 7 and 8). There was a statistically significant difference between the controls and the IBS subgroups (P &lt; 0.0001). The density of somatostatin cells was significantly lower in the IBS-D and IBS-M groups but higher in IBS-C patients than in the controls (P &lt; 0.01, P = 0.02, and P = 0.0008, respectively). The somatostatin cell density in patients with both IBS and FDP was 86 (0-194), and in those with IBS only 110 (0-206). There was no statistically significant difference between these 2 groups of patients (P = 0.6). There was no significant difference in somatostatin immunoreactivity intensity between the controls. The diarrhea score of the Birmingham IBS symptom questionnaire was inversely correlated with somatostatin cell density (r = 0.38; P = 0.0007) and was positively correlated with that of constipation (r = 0.64; P &lt; 0.0001).</p>
<p>CONCLUSION: The finding of abnormal endocrine cells in the oxyntic mucosa shows that the endocrine cell disturbances in IBS are not restricted to the intestine. Furthermore, it appears that ghrelin, serotonin and somatostatin in the oxyntic mucosa of the stomach may play an important role in the changing stool habits in IBS through their effects on intestinal motility.</p>
2014-05-01T00:00:00ZMolecular subtypes, histopathological grade and survival in a historic cohort of breast cancer patientshttp://hdl.handle.net/1956/10573
Molecular subtypes, histopathological grade and survival in a historic cohort of breast cancer patients
Engstrøm, Monica J; Opdahl, Signe; Hagen, Anne Irene; Romundstad, Pål Richard; Akslen, Lars A.; Haugen, Olav A.; Vatten, Lars Johan; Bofin, Anna M.
Journal article
Molecular subtyping of breast cancer may provide additional prognostic information regarding patient outcome. However, its clinical significance remains to be established. In this study, the main aims were to discover whether reclassification of breast cancer into molecular subtypes provides more precise information regarding outcome compared to conventional histopathological grading and to study breast cancer-specific survival in the different molecular subtypes. Cases of breast cancer occurring in a cohort of women born between 1886 and 1928 with long-term follow-up were included in the study. Tissue microarrays were constructed from archival formalin-fixed, paraffin-embedded tissue from 909 cases. Using immunohistochemistry and in situ hybridisation as surrogates for gene expression analyses, all cases were reclassified into the following molecular subtypes: Luminal A; Luminal B (HER2−); Luminal B (HER2+); HER2 subtype; Basal phenotype; and five negative phenotype. Kaplan–Meier survival curves and Cox proportional hazards models were used in the analyses. During the first 5 years after diagnosis, there were significant differences in prognosis according to molecular subtypes with the best survival for the Luminal A subtype and the worst for HER2 and five negative phenotype. In this historic cohort of women with breast cancer, differences in breast cancer-specific survival according to subtype occur almost exclusively amongst the histopathological grade 2 tumours. From 5 years after time of diagnosis until the end of follow-up, there appears to be no difference in survival according to molecular subtype or histopathological grade.
2013-08-01T00:00:00ZNothing to complain about? : residents’ and relatives’ viewson a "good life" and ethical challenges in nursing homeshttp://hdl.handle.net/1956/10564
Nothing to complain about? : residents’ and relatives’ viewson a "good life" and ethical challenges in nursing homes
Bollig, Georg; Gjengedal, Eva; Rosland, Jan Henrik
Journal article
Background: Nursing home residents are a vulnerable population. Most of them suffer from multimorbidity,
while many have cognitive impairment or dementia and need care around the clock. Several ethical
challenges in nursing homes have been described in the scientific literature. Most studies have used staff
members as informants, some have focused on the relatives’ view, but substantial knowledge about the
residents’ perspective is lacking.
Objective: To study what nursing home residents and their relatives perceive as ethical challenges in
Norwegian nursing homes.
Research design: A qualitative design with in-depth interviews with nursing home residents, and focusgroup
interviews with relatives of nursing home residents. The digitally recorded interviews were transcribed
verbatim. Analysis was based on Interpretive Description.
Participants and research context: A total of 25 nursing home residents from nine nursing homes in
Norway, and 18 relatives of nursing home residents from three of these nursing homes.
Ethical considerations: This study was reported to and approved by the Regional Ethics Committee in
Oslo, Norway.
Findings and discussion: The main ethical challenges in Norwegian nursing homes from the residents’
and relatives’ perspective were as follows: (a) acceptance and adaptation, (b) well-being and a good life,
(c) autonomy and self-determination, and (d) lack of resources. The relationship with the staff was of outmost
importance and was experienced as both rewarding and problematic. None of the residents in our
study mentioned ethical challenges connected to end-of-life care.
Conclusion: Residents and relatives experience ethical challenges in Norwegian nursing homes, mostly
connected to "everyday ethical issues."
2014-01-01T00:00:00ZCancer and Total Hip Replacement. Cancer as a risk factor for prosthesis and prosthesis as a risk factor for cancerhttp://hdl.handle.net/1956/10552
Cancer and Total Hip Replacement. Cancer as a risk factor for prosthesis and prosthesis as a risk factor for cancer
Dybvik, Eva Hansen
Doctoral thesis
<p>Annually, 14 million new cancer cases are detected worldwide; the numbers are
expected to rise by 70% over the next decades. In Norway, 30,000 new cancer cases
are detected every year. Because of screenings and increased attention to cancer in
the population, more cancer cases are detected at an early stage and a higher number
of cancer diagnoses are detected. Results of better and earlier treatment are that
patients survive and continue to live for many years after a cancer diagnosis.</p>
<p>In Western countries, total hip replacements have become a common treatment for
hip joint disease and injury. Standards of living have risen and people are living
longer, hence Western populations have an increased proportion of elderly people.
Better anaesthetics, lower risks associated with surgery and better quality of
prostheses enable both younger and older patients with good general health to receive
total hip replacements. In Norway almost 8,000 primary total hip replacement
operations are performed annually.</p>
<p>All papers in this thesis are based on a linkage between the Cancer Registry of
Norway and the Norwegian Arthroplasty Register.</p>
<p>In this thesis there are two different aspects. The first aspect is the cancer patients; if
they survive cancer and live on for many years, there is a risk for developing other
diseases and disorders. These may be late effects related to the treatment they
received for cancer. In this thesis we consider damage to bone and cartilage in the
hip. Our outcome measurement is the insertion of a total hip replacement.</p>
<p>The second aspect is the patients who have received a total hip replacement. Could
insertion of metal prosthesis with or without bone cement in the hip joint increase the
patient's risk for late development of cancer?</p>
<p>In Paper 1 we selected cancer patients who were 16-90 years old when their first
cancer was diagnosed, had no hip replacement prior to the cancer diagnosis and were
alive when the Norwegian Arthroplasty Register started registration (September 1987). We compared the observed hip replacement patients with incidence in the
general population. Cancer patients were divided in groups according to the location
of the cancer and compared. We found an increased risk for hip replacement for
patients with lymphoma malignancies and cancer in the pelvic area.</p>
<p>In Paper 2 we selected two groups of cancer patients to investigate whether radiation
to the pelvic area increased the risk for total hip replacement. We included women
only; one group consisted of patients with gynaecological cancer and radiation to the
pelvic area while the other group consisted of breast cancer patients with radiation to
the breast and not to the pelvic area. The mortality differed greatly in the two groups,
so we used competing risk models to estimate the risk for receiving prosthesis. We
found no statistically increased risk for hip replacements for patients with
gynaecological cancer compared to patients with breast cancer.</p>
<p>In Paper 3 we selected patients with total hip replacement. We compared their cancer
risk to the general population in Norway. We also used Cox models and competing
risk models with time-dependent covariates to compare different prosthesis fixations.
We found an increased risk of cancer for patients with uncemented total hip
replacement compared to patients with cemented total hip replacement. Patients with
a combination of cemented cup and uncemented stem (reversed hybrid) had a similar
risk for cancer as those with uncemented prosthesis.</p>
<p>The overall conclusion in this thesis is that we found a relation between cancer and
total hip replacements. There seems to be an increased risk for hip replacements for
some cancer types, but we could not find any increased risk due to irradiation of the
hips. For patients who have had a hip replacement for more than 10 years,
uncemented prosthesis seems to increase the risk of cancer.</p>
2015-09-18T00:00:00ZFailure rate of cemented and uncemented total hip replacements: register study of combined Nordic database of four nationshttp://hdl.handle.net/1956/10516
Failure rate of cemented and uncemented total hip replacements: register study of combined Nordic database of four nations
Mäkelä, Keijo T.; Matilainen, Markus; Pulkkinen, Pekka; Fenstad, Anne Marie; Havelin, Leif Ivar; Engesæter, Lars B.; Furnes, Ove; Pedersen, Alma B; Overgaard, Søren; Kärrholm, Johan; Malchau, Henrik; Garellick, Göran; Ranstam, Jonas; Eskelinen, Antti
Journal article
<p>Objective: To assess the failure rate of cemented, uncemented, hybrid, and reverse hybrid total hip replacements in patients aged 55 years or older.</p>
<p>Design: Register study.</p>
<p>Setting: Nordic Arthroplasty Register Association database (combined data from Sweden, Norway, Denmark, and Finland).</p>
<p>Participants: 347 899 total hip replacements performed during 1995-2011.</p>
<p>Main outcome measures: Probability of implant survival (Kaplan-Meier analysis) along with implant survival with revision for any reason as endpoint (Cox multiple regression) adjusted for age, sex, and diagnosis in age groups 55-64, 65-74, and 75 years or older.</p>
<p>Results: The proportion of total hip replacements using uncemented implants increased rapidly towards the end of the study period. The 10 year survival of cemented implants in patients aged 65 to 74 and 75 or older (93.8%, 95% confidence interval 93.6% to 94.0% and 95.9%, 95.8% to 96.1%, respectively) was higher than that of uncemented (92.9%, 92.3% to 93.4% and 93.0%, 91.8% to 94.0%), hybrid (91.6%, 90.9% to 92.2% and 93.9%, 93.1% to 94.5%), and reverse hybrid (90.7%, 87.3% to 93.2% and 93.2%, 90.7% to 95.1%) implants. The survival of cemented (92.2%, 91.8% to 92.5%) and uncemented (91.8%, 91.3% to 92.2%) implants in patients aged 55 to 64 was similar. During the first six months the risk of revision with cemented implants was lower than with all other types of fixation in all age groups.</p>
<p>Conclusion: The survival of cemented implants for total hip replacement was higher than that of uncemented implants in patients aged 65 years or older. The increased use of uncemented implants in this age group is not supported by these data. However, because our dataset includes only basic information common to all national registers there is potential for residual confounding.</p>
2014-01-01T00:00:00ZMale caregivers to persons diagnosed with Lewy Body Dementia have higher stress level than caregiver to persons diagnosed with Alzheimers Dementiahttp://hdl.handle.net/1956/10513
Male caregivers to persons diagnosed with Lewy Body Dementia have higher stress level than caregiver to persons diagnosed with Alzheimers Dementia
Svendsbø, Ellen J; Terum, Toril; Testad, Ingelin; Aarsland, Dag; Rongve, Arvid
Conference object
Poster presentation at AD/PD, Kenes International: International conference on Alzheimer's and Parkinson's diseases and related neurological disorders, 18.-22. March.
2015-01-01T00:00:00ZHemiarthroplasties after hip fractures in Norway and Sweden: A collaboration between the Norwegian and Swedish national registrieshttp://hdl.handle.net/1956/10511
Hemiarthroplasties after hip fractures in Norway and Sweden: A collaboration between the Norwegian and Swedish national registries
Gjertsen, Jan Erik; Fenstad, Anne Marie; Leonardsson, Olof; Engesæter, Lars B.; Kärrholm, Johan; Furnes, Ove; Garellick, Göran; Rogmark, Cecilia
Journal article
National registration of hemiarthroplasties after hip fractures has been established in both Norway and Sweden. We aimed to investigate differences in demographics, choice of implant selection, surgical approaches, and reoperations between the Norwegian Hip Fracture Register (NHFR) and the Swedish Hip Arthroplasty Register (SHAR). As part of the Nordic Arthroplasty Register Association (NARA) project a common hemiarthroplasty dataset has been established. 36,989 primary hemiarthroplasties (HAs) for acute hip fractures reported to NHFR (n = 12,761) and SHAR (n = 24,228) for the period 2005-2010 were included. Cemented prostheses were used in 78% of the operations in Norway and in 95% of the patients in Sweden. In Norway HAs almost exclusively had bipolar design (98%), whereas in Sweden HAs with unipolar design were used in 42% of the cases. Monoblock (non-modular) prostheses were uncommon, but still more frequently used in Sweden than in Norway (6.9% and 2.1% respectively). The lateral approach was more common in Norway (83%) than in Sweden (52%), where the posterior approach was used in 42% of the cases. The five-year survival of all HAs was 95.5% (95% CI: 94.8-96.2) in Norway and 94.8% (95% CI: 94.4-95.3) in Sweden. We concluded that surprisingly large differences between the two countries in demographics, implant design, and surgical technique had been revealed. This common dataset enables further investigations of the impact of these differences on revision rates and mortality.
2014-05-01T00:00:00ZIs irritable bowel syndrome an organic disorder?http://hdl.handle.net/1956/10507
Is irritable bowel syndrome an organic disorder?
El-Salhy, Magdy; Gundersen, Doris Irene; Gilja, Odd Helge; Hatlebakk, Jan G; Hausken, Trygve
Journal article
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is generally considered to be functional because there appears to be no associated anatomical defect. Stress and psychological factors are thought to play an important role in IBS. The gut neuroendocrine system (NES), which regulates all functions of the gastrointestinal tract, consists of endocrine cells that are scattered among the epithelial cells of the mucosa, and the enteric nervous system. Although it is capable of operating independently from the central nervous system (CNS), the gut NES is connected to and modulated by the CNS. This review presents evidence for the presence of an anatomical defect in IBS patients, namely in the gastrointestinal endocrine cells. These cells have specialized microvilli that project into the lumen and function as sensors for the luminal content and respond to luminal stimuli by releasing hormones into the lamina propria, which starts a chain reaction that progresses throughout the entire NES. The changes in the gastrointestinal endocrine cells observed in IBS patients are highly consistent with the other abnormalities reported in IBS patients, such as visceral hypersensitivity, dysmotility, and abnormal secretion.
2014-01-14T00:00:00ZA critical review of pro-cognitive drug targets in psychosis: convergence on myelination and inflammationhttp://hdl.handle.net/1956/10506
A critical review of pro-cognitive drug targets in psychosis: convergence on myelination and inflammation
Kroken, Rune; Løberg, Else-Marie; Drønen, Tore; Grüner, Renate; Hugdahl, Kenneth; Kompus, Kristiina; Skrede, Silje; Johnsen, Erik
Journal article
Antipsychotic drugs have thus far focused on dopaminergic antagonism at the D2 receptors, as counteracting the hyperdopaminergia in nigrostriatal and mesolimbic projections has been considered mandatory for the antipsychotic action of the drugs. Current drugs effectively target the positive symptoms of psychosis such as hallucinations and delusions in the majority of patients, whereas effect sizes are smaller for negative symptoms and cognitive dysfunctions. With the understanding that neurocognitive dysfunction associated with schizophrenia have a greater impact on functional outcome than the positive symptoms, the focus in pharmacotherapy for schizophrenia has shifted to the potential effect of future drugs on cognitive enhancement. A major obstacle is, however, that the biological underpinnings of cognitive dysfunction remain largely unknown. With the availability of increasingly sophisticated techniques in molecular biology and brain imaging, this situation is about to change with major advances being made in identifying the neuronal substrates underlying schizophrenia, and putative pro-cognitive drug targets may be revealed. In relation to cognitive effects, this review focuses on evidence from basic neuroscience and clinical studies, taking two separate perspectives. One perspective is the identification of previously under-recognized treatment targets for existing antipsychotic drugs, including myelination and mediators of inflammation. A second perspective is the development of new drugs or novel treatment targets for well-known drugs, which act on recently discovered treatment targets for cognitive enhancement, and which may complement the existing drugs. This might pave the way for personalized treatment regimens for patients with schizophrenia aimed at improved functional outcome. The review also aims at identifying major current constraints for pro-cognitive drug development for patients with schizophrenia.
2014-02-04T00:00:00ZEndocrine cells in the ileum of patients with irritable bowel syndromehttp://hdl.handle.net/1956/10505
Endocrine cells in the ileum of patients with irritable bowel syndrome
El-Salhy, Magdy; Gilja, Odd Helge; Gundersen, Doris Irene; Hatlebakk, Jan G; Hausken, Trygve
Journal article
<p>AIM: To study the ileal endocrine cell types in irritable bowel syndrome (IBS) patients.</p>
<p>METHODS: Ninety-eight patients with IBS (77 females and 21 males; mean age 35 years, range 18-66 years) were included, of which 35 patients had diarrhea (IBS-D), 31 patients had a mixture of both diarrhea and constipation (IBS-M), and 32 patients had constipation (IBS-C) as the predominant symptoms. The controls were 38 subjects (26 females and 12 males; mean age 40 years, range 18-65 years) who had submitted to colonoscopy for the following reasons: gastrointestinal bleeding, where the source of bleeding was identified as hemorrhoids (n = 24) or angiodysplasia (n = 3), and health worries resulting from a relative being diagnosed with colon carcinoma (n = 11). The patients were asked to complete the: Birmingham IBS symptom questionnaire. Ileal biopsy specimens from all subjects were immunostained using the avidin-biotin-complex method for serotonin, peptide YY (PYY), pancreatic polypeptide (PP), enteroglucagon, and somatostatin cells. The cell densities were quantified by computerized image analysis, using Olympus cellSens imaging software.</p>
<p>RESULTS: The gender and age distributions did not differ significantly between the patients and the controls (P = 0.27 and P = 0.18, respectively). The total score of Birmingham IBS symptom questionnaire was 21 &plusmn; 0.8, and the three underlying dimensions: pain, diarrhea, and constipation were 7.2 &plusmn; 0.4, 6.6 &plusmn; 0.4, and 7.2 &plusmn; 0.4, respectively. The density of serotonin cells in the ileum was 40.6 &plusmn; 3.6 cells/mm2 in the controls, and 11.5 &plusmn; 1.2, 10.7 &plusmn; 5.6, 10.0 &plusmn; 1.9, and 13.9 &plusmn; 1.4 cells/mm2 in the all IBS patients (IBS-total), IBS-D, IBS-M, and IBS-C patients, respectively. The density in the controls differed significantly from those in the IBS-total, IBS-D, IBS-M, and IBS-C groups (P &lt; 0.0001, P = 0.0001, P = 0.0001, and P &lt; 0.0001, respectively). There was a significant inverse correlation between the serotonin cell density and the pain dimension of Birmingham IBS symptom questionnaire (r = -0.6, P = 0.0002). The density of PYY cells was 26.7 &plusmn; 1.6 cells/mm2 in the controls, and 33.1 &plusmn; 1.4, 27.5 &plusmn; 1.4, 34.1 &plusmn; 2.5, and 41.7 &plusmn; 3.1 cells/mm2 in the IBS-total, IBS-D, IBS-M, and IBS-C patients, respectively. This density differed significantly between patients with IBS-total and IBS-C and the controls (P = 0.03 and &lt; 0.0001, respectively), but not between controls and, IBS-D, and IBS-M patients (P = 0.8, and P = 0.1, respectively). The density of PYY cells correlated significantly with the degree of constipation as recorded by the Birmingham IBS symptom questionnaire (r = 0.6, P = 0.0002). There were few PP-, enteroglucagon-, and somatostatin-immunoreactive cells in the biopsy material examined, which made it impossible to reliably quantify these cells.</p>
<p>CONCLUSION: The decrease of ileal serotonin cells is associated with the visceral hypersensitivity seen in all IBS subtypes. The increased density of PYY cells in IBS-C might contribute to the constipation experienced by these patients.</p>
2014-03-07T00:00:00ZChromogranin A cells in the stomachs of patients With sporadic irritable bowel syndromehttp://hdl.handle.net/1956/10503
Chromogranin A cells in the stomachs of patients With sporadic irritable bowel syndrome
El-Salhy, Magdy; Gilja, Odd Helge; Hausken, Trygve
Journal article
Several abnormalities have been demonstrated in the intestines of patients with irritable bowel syndrome (IBS); however, the endocrine cells in the stomachs of these patients have not been investigated. The aim of the present study was to determine whether there are any abnormalities in the endocrine cells of the stomachs of patients with IBS using chromogranin A (CgA) as a common marker for endocrine cells. A total of 76 patients were included, of which 26 presented with diarrhoea as the predominant symptom (IBS‑D), 21 exhibited diarrhoea and constipation (IBS‑M), and 29 experienced constipation as the predominant symptom (IBS‑C). In addition, 59 healthy volunteers were recruited as controls. The patients and the controls underwent gastroscopy, and biopsy samples were obtained from the antrum and corpus of the stomach. The biopsy samples were immunostained and the CgA‑positive cell density and the intensity of the CgA immunoreactivity were determined. The CgA‑positive cell densities in the antra of patients with IBS‑M were significantly reduced relative to the controls (P<0.01), while the densities were significantly increased in the antra and corpora of the IBS‑C patients (P<0.01 and P<0.001 respectively). The intensities of CgA immunoreactivity did not differ significantly between the IBS patients and the controls. The abnormalities in the densities of endocrine cells were not associated with concomitant changes in the intensities of immunoreactivity; this may indicate unchanged synthesis and/or release of the hormones. In conclusion, the difference in the density of endocrine cells among the IBS subtypes may reflect a role of these cells in the differential symptomologies of these subtypes.
2014-10-01T00:00:00ZInteraction between ingested nutrients and gut endocrine cells in patients with irritable bowel syndrome (Review)http://hdl.handle.net/1956/10500
Interaction between ingested nutrients and gut endocrine cells in patients with irritable bowel syndrome (Review)
El-Salhy, Magdy; Gilja, Odd Helge; Gundersen, Doris Irene; Hatlebakk, Jan G; Hausken, Trygve
Journal article
Several endocrine cell abnormalities have been reported in different segments of the gastrointestinal tract of patients with irritable bowel syndrome (IBS). These cells have specialized microvilli that project into the lumen; they function as sensors for the gut contents and respond to luminal stimuli (mostly ingested nutrients) by releasing hormones into the lamina propria, where they exert their effects via a paracrine/endocrine mode of action. Certain food items trigger the symptoms experienced by IBS patients, including those rich in fermentable oligo-, di- and monosaccharides, and polyols (FODMAPs). In this review, we present the argument that the effects of both FODMAPs and the proportional intake of proteins, fats and carbohydrates on IBS symptoms may be caused by an interaction with the gut endocrine cells. Since the gut hormones control and regulate gastrointestinal motility and sensation, this interaction may be responsible for abnormal gastrointestinal motility and the visceral hypersensitivity observed in these patients. There is no consistent evidence that IBS patients suffer from food allergy. The role of gluten intolerance in the development of IBS symptoms in these patients remains a matter of controversy. Individual guidance on food management, which includes restrictions in the intake of FODMAP-rich foods and testing diets with different proportions of proteins, fats and carbohydrates has been found to reduce the symptoms, improve the quality of life, and make the habitual diet of IBS patients more healthy.
2014-08-01T00:00:00ZMetabolic alkalosis is the most common acid-base disorder in ICU patientshttp://hdl.handle.net/1956/10487
Metabolic alkalosis is the most common acid-base disorder in ICU patients
Mæhle, Kirsten Vikesland; Haug, Bjørn; Flaatten, Hans; Nielsen, Erik Waage
Journal article
2014-03-28T00:00:00ZSatisfaction with life during pregnancy and early motherhood in first-time mothers of advanced age: A population-based longitudinal studyhttp://hdl.handle.net/1956/10463
Satisfaction with life during pregnancy and early motherhood in first-time mothers of advanced age: A population-based longitudinal study
Aasheim, Vigdis; Waldenström, Ulla; Rasmussen, Svein; Espehaug, Birgitte; Schytt, Erica
Journal article
<p>Background: The trend to delay motherhood to the age of 30 and beyond is established in most high-income countries but relatively little is known about potential effects on maternal emotional well-being. This study investigates satisfaction with life during pregnancy and the first three years of motherhood in women expecting their first baby at an advanced and very advanced age.</p>
<p>Methods: The study was based on the National Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health. Data on 18 565 nulliparous women recruited in the second trimester 1999&ndash;2008 were used. Four questionnaires were completed: at around gestational weeks 17 and 30, and at six months and three years after the birth. Medical data were retrieved from the national Medical Birth Register. Advanced age was defined as 32&ndash;37 years, very advanced age as &ge;38 years and the reference group as 25&ndash;31 years. The distribution of satisfaction with life from age 25 to &ge;40 years was investigated, and the mean satisfaction with life at the four time points was estimated. Logistic regression analyses based on generalised estimation equations were used to investigate associations between advanced and very advanced age and satisfaction with life when controlling for socio-demographic factors.</p>
<p>Results: Satisfaction with life decreased from around age 28 to age 40 and beyond, when measured in gestational weeks 17 and 30, and at six months and three years after the birth. When comparing women of advanced and very advanced age with the reference group, satisfaction with life was slightly reduced in the two older age groups and most of all in women of very advanced age. Women of very advanced age had the lowest scores at all time points and this was most pronounced at three years after the birth.</p>
<p>Conclusion: First-time mothers of advanced and very advanced age reported a slightly lower degree of satisfaction with life compared with the reference group of younger women, and the age-related effect was greatest when the child was three years of age.</p>
2014-02-25T00:00:00ZPosterior approach and uncemented stems increases the risk of reoperation after hemiarthroplasties in elderly hip fracture patientshttp://hdl.handle.net/1956/10462
Posterior approach and uncemented stems increases the risk of reoperation after hemiarthroplasties in elderly hip fracture patients
Rogmark, Cecilia; Fenstad, Anne Marie; Leonardsson, Olof; Engesæter, Lars B.; Kärrholm, Johan; Furnes, Ove; Garellick, Göran; Gjertsen, Jan Erik
Journal article
<p>Background &mdash; Hemiarthroplasties are performed in great numbers worldwide but are seldom registered on a national basis. Our aim was to identify risk factors for reoperation after fracturerelated hemiarthroplasty in Norway and Sweden.</p>
<p>Material and methods &mdash; A common dataset was created based on the Norwegian Hip Fracture Register and the Swedish Hip Arthroplasty Register. 33,205 hip fractures in individuals &gt; 60 years of age treated with modular hemiarthroplasties were reported for the period 2005&ndash;2010. Cox regression analyses based on reoperations were performed (covariates: age group, sex, type of stem and implant head, surgical approach, and hospital volume).</p>
<p>Results &mdash; 1,164 patients (3.5%) were reoperated during a mean follow-up of 2.7 (SD 1.7) years. In patients over 85 years, an increased risk of reoperation was found for uncemented stems (HR = 2.2, 95% CI: 1.7&ndash;2.8), bipolar heads (HR = 1.4, CI: 1.2&ndash;1.8), posterior approach (HR = 1.4, CI: 1.2&ndash;1.8) and male sex (HR = 1.3, CI: 1.0&ndash;1.6). For patients aged 75&ndash;85 years, uncemented stems (HR = 1.6, 95% CI: 1.2&ndash;2.0) and men (HR = 1.3, CI: 1.1&ndash;1.6) carried an increased risk. Increased risk of reoperation due to infection was found for patients aged &lt; 75 years (HR = 1.5, CI: 1.1&ndash;2.0) and for uncemented stems. For open surgery due to dislocation, the strongest risk factor was a posterior approach (HR = 2.2, CI: 1.8&ndash;2.6). Uncemented stems in particular (HR = 3.6, CI: 2.4&ndash;5.3) and male sex increased the risk of periprosthetic fracture surgery.</p>
<p>Interpretation &mdash; Cemented stems and a direct lateral transgluteal approach reduced the risk of reoperation after hip fractures treated with hemiarthroplasty in patients over 75 years. Men and younger patients had a higher risk of reoperation. For the age group 60&ndash;74 years, there were no such differences in risk in this material.</p>
2014-01-01T00:00:00ZWorse patient-reported outcome after lateral approach than after anterior and posterolateral approach in primary hip arthroplastyhttp://hdl.handle.net/1956/10454
Worse patient-reported outcome after lateral approach than after anterior and posterolateral approach in primary hip arthroplasty
Amlie, Einar Johan Braém; Havelin, Leif Ivar; Furnes, Ove; Baste, Valborg; Nordsletten, Lars; Høvik, Øystein; Dimmen, Sigbjørn
Journal article
<p>Background &mdash; The surgical approach in total hip arthroplasty (THA) is often based on surgeon preference and local traditions. The anterior muscle-sparing approach has recently gained popularity in Europe. We tested the hypothesis that patient satisfaction, pain, function, and health-related quality of life (HRQoL) after THA is not related to the surgical approach.</p>
<p>Patients &mdash; 1,476 patients identified through the Norwegian Arthroplasty Register were sent questionnaires 1&ndash;3 years after undergoing THA in the period from January 2008 to June 2010. Patient-reported outcome measures (PROMs) included the hip disability osteoarthritis outcome score (HOOS), the Western Ontario and McMaster Universities osteoarthritis index (WOMAC), health-related quality of life (EQ-5D-3L), visual analog scales (VAS) addressing pain and satisfaction, and questions about complications. 1,273 patients completed the questionnaires and were included in the analysis.</p>
<p>Results &mdash; Adjusted HOOS scores for pain, other symptoms, activities of daily living (ADL), sport/recreation, and quality of life were significantly worse (p &lt; 0.001 to p = 0.03) for the lateral approach than for the anterior approach and the posterolateral approach (mean differences: 3.2&ndash;5.0). These results were related to more patient-reported limping with the lateral approach than with the anterior and posterolateral approaches (25% vs. 12% and 13%, respectively; p &lt; 0.001).</p>
<p>Interpretation &mdash; Patients operated with the lateral approach reported worse outcomes 1&ndash;3 years after THA surgery. Self-reported limping occurred twice as often in patients who underwent THA with a lateral approach than in those who underwent THA with an anterior or posterolateral approach. There were no significant differences in patient-reported outcomes after THA between those who underwent THA with a posterolateral approach and those who underwent THA with an anterior approach.</p>
2014-01-01T00:00:00ZHigher revision risk for unicompartmental knee arthroplasty in low-volume hospitalshttp://hdl.handle.net/1956/10445
Higher revision risk for unicompartmental knee arthroplasty in low-volume hospitals
Badawy, Mona; Espehaug, Birgitte; Indrekvam, Kari; Havelin, Leif Ivar; Furnes, Ove
Journal article
<p>Background and purpose &mdash; Some studies have found high complication rates and others have found low complication rates after unicompartmental knee arthroplasty (UKA). We evaluated whether hospital procedure volume influences the risk of revision using data from the Norwegian Arthroplasty Register (NAR).</p>
<p>Materials and methods &mdash; 5,791 UKAs have been registered in the Norwegian Arthroplasty Register. We analyzed the 4,460 cemented medial Oxford III implants that were used from 1999 to 2012; this is the most commonly used UKA implant in Norway. Cox regression (adjusted for age, sex, and diagnosis) was used to estimate risk ratios (RRs) for revision. 4 different volume groups were compared: 1&ndash;10, 11&ndash;20, 21&ndash;40, and &gt; 40 UKA procedures annually per hospital. We also analyzed the reasons for revision.</p>
<p>Results and interpretation &mdash; We found a lower risk of revision in hospitals performing more than 40 procedures a year than in those with less than 10 UKAs a year, with an unadjusted RR of 0.53 (95% CI: 0.35&ndash;0.81) and adjusted RR of 0.59 (95% CI: 0.39&ndash;0.90). Low-volume hospitals appeared to have a higher risk of revision due to dislocation, instability, malalignment, and fracture than high-volume hospitals.</p>
2014-01-01T00:00:00ZMolecular pathogenesis of polymerase gamma-related neurodegenerationhttp://hdl.handle.net/1956/10444
Molecular pathogenesis of polymerase gamma-related neurodegeneration
Tzoulis, Charalampos; Tran, Gia Tuong Thi; Coxhead, Jonathan; Bertelsen, Bjørn; Lilleng, Peer Kåre; Balafkan, Novin; Payne, Brendan; Miletic, Hrvoje; Chinnery, Patrick F.; Bindoff, Laurence
Journal article
<p>Objective: Polymerase gamma (POLG) mutations are a common cause of mitochondrial disease and have also been linked to neurodegeneration and aging. We studied the molecular mechanisms underlying POLG-related neurodegeneration using postmortem tissue from a large number of patients.</p>
<p>Methods: Clinical information was available from all subjects. Formalin-fixed and frozen brain tissue from 15 patients and 23 controls was studied employing a combination of histopathology, immunohistochemistry, and molecular studies of microdissected neurons.</p>
<p>Results: The primary consequence of POLG mutation in neurons is mitochondrial DNA depletion. This was already present in infants with little evidence of neuronal loss or mitochondrial dysfunction. With longer disease duration, we found an additional, progressive accumulation of mitochondrial DNA deletions and point mutations accompanied by increasing numbers of complex I&ndash;deficient neurons. Progressive neurodegeneration primarily affected the cerebellar systems and dopaminergic cells of the substantia nigra. Superimposed on this chronic process were acute, focal cortical lesions that correlated with epileptogenic foci and that showed massive neuronal loss.</p>
<p>Interpretation: POLG mutations appear to compromise neuronal respiration via a combination of early and stable depletion and a progressive somatic mutagenesis of the mitochondrial genome. This leads to 2 distinct but overlapping biological processes: a chronic neurodegeneration reflected clinically by progressive ataxia and cognitive impairment, and an acute focal neuronal necrosis that appears to be related to the presence of epileptic seizures. Our findings offer an explanation of the acute-on-chronic clinical course of this common mitochondrial encephalopathy.</p>
2014-07-01T00:00:00ZStomach antral endocrine cells in patients with irritable bowel syndromehttp://hdl.handle.net/1956/10438
Stomach antral endocrine cells in patients with irritable bowel syndrome
El-Salhy, Magdy; Gilja, Odd Helge; Hatlebakk, Jan G; Hausken, Trygve
Journal article
To the best of our knowledge, stomach antral endocrine cells have not previously been investigated in patients with irritable bowel syndrome (IBS). Thus, in the present study, 76 patients with IBS were examined (designated as IBS-total). Diarrhoea was the predominant symptom in 26 of these patients (IBS-D), while in 21 patients, the predominant symptoms were both diarrhoea and constipation (IBS-M) and in 29 patients the predominant symptom was constipation (IBS-C). Forty-three healthy subjects were enrolled as the controls. Stomach antral biopsy samples obtained from all of the subjects were immunostained using the avidin-biotin-complex method for serotonin, gastrin, somatostatin and serotonin transporter (SERT). The immunopositive cell densities and immunoreactivity intensities were determined by computer-aided image analysis. The density of the serotonin-immunoreactive cells was significantly decreased in the IBS-M patients and increased in the IBS-C patients relative to the controls. The immunoreactivity intensity did not differ significantly between the controls and IBS-total. The density of the gastrin-immunoreactive cells was significantly greater in the IBS-D, IBS-M and IBS-C patients than in the controls. The immunoreactivity intensity of gastrin was significantly greater in the IBS-D patients than in the controls. The density of the somatostatin-immunoreactive cells cells was significantly lower in the IBS-total, IBS-D, IBS-M and IBS-C patients than in the controls. The immunoreactivity intensities of both somatostatin and SERT did not differ significantly between the controls and IBS-total. The increase in gastrin cell density and the decrease in somatostatin cell density in all IBS subtypes may cause high levels of gastric secretion, which may in turn contribute to the high incidence of dyspepsia and gastro-oesophageal reflux observed in patients with IBS.
2014-10-01T00:00:00ZThe Role of Diet in Irritable Bowel Syndrome with special reference to Gut Neuroendocrine Systemhttp://hdl.handle.net/1956/10371
The Role of Diet in Irritable Bowel Syndrome with special reference to Gut Neuroendocrine System
Mazzawi, Tarek
Doctoral thesis
<p>Background: The majority of the patients with irritable bowel syndrome (IBS)
believe that diet triggers their symptoms, which affect the quality of their lives. The
pathophysiology of IBS is not exactly known, however, the endocrine cells of the gut,
which are known to regulate most of the functions of the gastrointestinal tract, are
believed to play an important role in the IBS pathophysiology. These cells have been
found abnormal in the patients with IBS. These endocrine cells extend their microvilli
to the gut lumen and sense its contents, particularly nutrients, and release gut
hormones in response to the events taking place in the gut lumen.</p>
<p>Aim: The overall aim has been to investigate the effect of dietary guidance with
reduced intake of fermentable oligo-, di-, monosaccharides and polyols (FODMAPs)
on:
1. IBS symptoms.
2. The quality of life of IBS patients.
3. To elucidate whether the changes in symptoms and quality of life brought by
dietary guidance are accompanied by alterations in the gastrointestinal endocrine cells.</p>
<p>Materials and methods: Forty-six patients who fulfilled the Rome III criteria for the
diagnosis of IBS were included in the study. All the patients were asked to complete
the following questionnaires to assess their symptoms, quality of life and habitual
dietary intake: The Birmingham IBS symptom score questionnaire, the IBS Quality of
Life (IBS-QOL) questionnaire, the Short-Form Nepean and Dyspepsia Index
(SF-NDI) and the MoBa Food Frequency Questionnaire (MoBa FFQ). They also
underwent gastroscopy with biopsies taken from the corpus and the antrum of the
stomach and colonoscopy with biopsies taken from the colon and the rectum to exclude other organic diseases. Then the patients attended three sessions,
approximately 45 minutes each, of guidance on dietary management with a registered
nurse. Of these patients, only 17 patients remained during the whole study and were
asked to strictly follow a diet as prescribed in the dietary guidance for at least 3
months. Thereafter, they were asked to complete a second set of the same
questionnaires for comparison. Fourteen out of the 17 patients underwent a second
gastroscopy with biopsy samples taken from the corpus and antrum of the stomach
and 13 out of the 17 patients underwent a second colonoscopy with biopsy samples
taken from the colon and the rectum. As controls, 14 healthy subjects were included
and underwent gastroscopy with biopsy sampling same as the patients. Only 13 out of
the 14 controls underwent colonoscopy with biopsy sampling similar to the ones taken
from the patients. The biopsy samples were immunostained using the Avidin-biotin-
Complex method for all of the endocrine cell types in the stomach and the large
intestine and were quantified by computerized image analysis.</p>
<p>Results: The findings are summarized as follows:
In paper I, the patients reported an improvement in their quality of life as assessed by
IBS-QOL and the SF-NDI questionnaires and a reduction in the total IBS symptoms
as assessed by the Birmingham IBS symptom score questionnaire. There was a
reduction in the consumption of food items rich with FODMAPs and an increase in
the consumption of some minerals and vitamins.
In paper II, IBS patients had low densities of chromogranin A (CgA) in the stomach.
These densities increased in these patients following dietary guidance towards the
levels of healthy controls.
In paper III, the densities of all the endocrine cells in the stomach of IBS patients were
abnormal before receiving dietary guidance. These densities changed towards the
values of healthy controls after receiving dietary guidance.
In paper IV, IBS patients represented low densities of CgA in the colon and were
increased towards the values of healthy controls following dietary guidance. The densities of CgA in the rectum were unchanged before and after receiving dietary
guidance.
In paper V, the densities of the endocrine cells in the colon of IBS patients were
abnormal before dietary guidance. Following dietary guidance, the densities of the
endocrine cells tend to normalize in the colon, however, in the rectum; the densities of
the endocrine cells remained unchanged.</p>
<p>Conclusions:
Three sessions of dietary guidance reduced the symptoms of IBS patients and
improved their quality of life. Through dietary guidance, the patients made correct
choices in consuming a FODMAP-poor diet yet maintaining adequate intake of
minerals and vitamins that were, otherwise, known to be deficient in IBS patients
without guidance. The densities of the endocrine cells in the stomach and the large
intestine that were abnormal before dietary guidance tend to normalize following
dietary guidance, thus reducing IBS symptoms and improving the quality of life of the
patients. The findings emphasized the interactions between food and the endocrine
cells of the gut and showed the positive effects of dietary guidance on the symptoms
of IBS patients, which may be attributed to changes in the densities of the endocrine
cells of the gut.</p>
2015-08-28T00:00:00ZIncreased chromogranin A cell density in the large intestine of patients with irritable bowel syndrome after receiving dietary guidancehttp://hdl.handle.net/1956/10370
Increased chromogranin A cell density in the large intestine of patients with irritable bowel syndrome after receiving dietary guidance
Mazzawi, Tarek; Gundersen, Doris Irene; Hausken, Trygve; El-Salhy, Magdy
Journal article
The large intestine contains five types of endocrine cells that regulate its functions by sensing its luminal contents and releasing specific hormones. Chromogranin A (CgA) is a common marker for the gastrointestinal endocrine cells, and it is abnormal in irritable bowel syndrome (IBS) patients. Most IBS patients relate their symptoms to certain food elements. The present study investigated the effect of dietary guidance on the total endocrine cells of the large intestine as detected by CgA in 13 IBS patients. Thirteen control subjects were also included. Each patient received three sessions of dietary guidance. Colonoscopies were performed on controls and patients (at baseline and at 3–9 months after receiving guidance). Biopsy samples from the colon and rectum were immunostained for CgA and quantified by computerized image analysis. The densities of CgA cells in the total colon (mean ± SEM) among the controls and the IBS patients before and after receiving dietary guidance were 83.3 ± 10.1, 38.6 ± 3.7, and 64.7 ± 4.2 cells/mm², respectively (P = 0.0004), and were unchanged in the rectum. In conclusion, the increase in CgA cell density after receiving dietary guidance may reflect a change in the densities of the large intestinal endocrine cells causing an improvement in the IBS symptoms.
2015-01-01T00:00:00ZEffects of dietary guidance on the symptoms, quality of life and habitual dietary intake of patients with irritable bowel syndromehttp://hdl.handle.net/1956/10369
Effects of dietary guidance on the symptoms, quality of life and habitual dietary intake of patients with irritable bowel syndrome
Mazzawi, Tarek; Hausken, Trygve; Gundersen, Doris Irene; El-Salhy, Magdy
Journal article
Diet is important in triggering the symptoms of irritable bowel syndrome (IBS). This study investigated the impact of dietary guidance on the symptoms, quality of life and habitual diet of patients with IBS. Forty‑six patients who fulfilled the Rome III criteria for the diagnosis of IBS were included. Of these patients, 17 completed the entire study. Each patient attended three sessions (~45 min in duration) and received individual guidance on their dietary management. The patients were asked to complete the following questionnaires prior to receiving the dietary guidance, and at least 3 months subsequently: The Birmingham IBS symptom score questionnaire, the IBS Quality of Life (IBS‑QOL) questionnaire, the Short‑Form Nepean and Dyspepsia Index (SF‑NDI) and the MoBa Food Frequency Questionnaire (MoBa FFQ). The time at which patients completed the questionnaires following dietary guidance ranged from 3‑9 months (median, 4 months). The total IBS symptom scores were reduced once the patients had received dietary guidance (P=0.001). The total score for the quality of life, as assessed by the IBS‑QOL and the SF‑NDI, increased significantly following the dietary guidance sessions (P=0.003 and P=0.002, respectively). There were no statistical differences in the intake of calories, carbohydrate, fiber, protein, fat or alcohol in the patients with IBS following dietary guidance. There were increases in the consumption of dairy products, β‑carotene, retinol equivalents, riboflavin, vitamin B12 and calcium, although only the increase in vitamin B12 consumption was statistically significant. There was a significant reduction in the consumption of certain fruits and vegetables that were rich in highly fermentable short‑chain carbohydrates, disaccharides, monosaccharides and polyols, as well as insoluble fibers. In conclusion, three 45-min dietary guidance sessions, administered by a nurse, reduced the symptoms and improved the quality of life of patients with IBS, and resulted in an adequate intake of vitamins and minerals. Individual dietary guidance is a cost‑effective option for the management of IBS.
2013-09-01T00:00:00ZDeveloping a novel femoral stem in hip arthroplasty. An innovation process using a weight-bearing animal modelhttp://hdl.handle.net/1956/10366
Developing a novel femoral stem in hip arthroplasty. An innovation process using a weight-bearing animal model
Harboe, Knut
Doctoral thesis
<p>Introduction:
To address the growing incidence of hip replacement revision, this project aimed to
find a stem that would fulfil three criteria. First, solid osteointegration and long
survival of the implant. Second, easy removal, if deemed necessary. Third, little or no
bone loss at the time of revision to facilitate the implantation of the revision stem.</p>
<p>Methods:
A stem of our own design was implanted in two animal series. Study 1 was
performed in 2006, and 12 goats were operated upon. Study 2 was performed in 2008
and included 35 goats. In both studies, the goats were observed for 6 months, and full
weight-bearing was permitted. After the goats were euthanised, the stems were
randomised to drilling or no drilling of the area of osteointegration and tested
biomechanically for differences in pull-out force. In Study 1, the implants were
coated with calcium phosphate (CP); in Study 2, hydroxyapatite (HA) was used
instead. Histological analysis was performed in both studies.</p>
<p>Results:
A significantly lower pull-out force was observed in Study 2 after drilling in the area
of osteointegration (mean, 1526 N vs. 2033 N, p = 0.028). The calcium phosphate
coating was inferior in performance to hydroxyapatite regarding bone apposition and
pull-out force (CP mean, 174 N vs. HA 1526 N, p = 0.003). No correlation of the
bone apposition evaluated by histology and pull-out force was observed. In addition,
there were no signs of inflammation.</p>
<p>Conclusion:
A significant effect of drilling longitudinally orientated grooves in a femoral stem in
goats to reduce pull-out force was observed. The hydroxyapatite coating appears
preferable to calcium phosphate on TiAl6V4-loaded implants with respect to bone
apposition and pull-out force. Bone growth towards the femoral stem was not
correlated with the pull-out force of the implant.</p>
2015-08-20T00:00:00Z